International Journal Of Clinical Pharmacology And Therapeutics[JOURNAL]
Sun
200 papers
Aplastic anemia associated with osimertinib: Analysis of the FDA adverse event reporting system.
Ohyama K, Katagiri S, Takahashi S … +5 more , Ayuhara H, Takeuchi H, Akahane D, Gotoh A, Hori Y
Int J Clin Pharmacol Ther · 2025 Jan · PMID 39565078 · Publisher ↗
OBJECTIVE: Aplastic anemia (AA) is a life-threatening disease, and drug-induced AA is rare. Recently, studies on cases that possibly developed AA following osimertinib treatment have been conducted. This study evaluated...
OBJECTIVE: Aplastic anemia (AA) is a life-threatening disease, and drug-induced AA is rare. Recently, studies on cases that possibly developed AA following osimertinib treatment have been conducted. This study evaluated the association of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including osimertinib, with AA and characterized such registered patients using a large spontaneous adverse event reporting database. MATERIALS AND METHODS: Data from the Food and Drug Administration's Adverse Event Reporting System spanning from the first quarter of 2015 to the second quarter of 2023 were used. Disproportionality analyses with reporting odds ratio (ROR) and information component (IC) were performed for signal detection. Furthermore, we described a case series of patients who experienced AA during osimertinib treatment. RESULTS: A signal was detected with osimertinib (ROR: 4.16, 95% confidence interval (CI): 2.54 - 6.80; IC: 1.80, 95% CI: 1.10 - 2.51); however, no signals were detected with other EGFR-TKIs. 16 individuals treated with osimertinib had AA, of whom 14 (87.5%) were registered as suspected drugs. The median age of these individuals was 70.5 years (interquartile range (IQR), 64.8 - 78.3 years), with varying time to onset (IQR, 4 - 210 days) and outcomes, including 3 (18.8%) deaths. CONCLUSION: Our analyses generated a safety signal for the association between osimertinib and AA. Further studies are required to understand and confirm the role of osimertinib administration in the development of AA.
The association between alphablockers in the treatment of benign prostatic hyperplasia and heart failure: A nationwide population-based cohort study in South Korea.
Jeong JY, Kim MK, Shin JY
Int J Clin Pharmacol Ther · 2025 Jan · PMID 39565077 · Publisher ↗
BACKGROUND AND OBJECTIVES: This study aimed to determine whether there is an association between the use of α-blockers to treat benign prostatic hyperplasia (BPH) and the development of heart failure in elderly Asian pat...
BACKGROUND AND OBJECTIVES: This study aimed to determine whether there is an association between the use of α-blockers to treat benign prostatic hyperplasia (BPH) and the development of heart failure in elderly Asian patients. MATERIALS AND METHODS: An Elderly Cohort Database of the National Health Insurance Service was used to select 22,540 patients with newly diagnosed BPH between January 1, 2008, and December 31, 2018. They were divided into two equal groups, one prescribed α-blockers and one not. They were followed up through December 31, 2019. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the occurrence of heart failure with α-blockers. In addition, α-blockers were categorized according to α1a receptor selectivity to estimate the hazard ratios for heart failure. RESULTS: Heart failure occurred in 283 patients in the non-user group and 74 patients in the α-blocker group, with an incidence rate of 553.4 in the non-user group and 516.8 in the α-blocker group per 100,000 person-years. Although α-blocker users had a higher hazard ratio for heart failure compared to the non-user group, this was not statistically significant (HR: α-blocker HR 1.14, 95% CI 0.87 - 1.491). Furthermore, when α-blockers were stratified by selectivity, the results were also not statistically significant (non-selective α-blocker HR 0.86, 95% CI 0.31 - 2.36). CONCLUSION: In this nationwide, population-based cohort study, treatment with α-blockers was not associated with the incidence of heart failure in patients with BPH.
Pharmacokinetics and bioequivalence of ezetimibe tablet in healthy Chinese subjects under fasting and fed conditions.
Liu G, Yan H, Yuan B … +1 more , Li G
Int J Clin Pharmacol Ther · 2025 Jan · PMID 39474818 · Publisher ↗
OBJECTIVE: The purpose of this study is to evaluate the pharmacokinetics (PK) parameters of an ezetimibe 10 mg (test drug) and assess its bioequivalence to the branded reference product in healthy Chinese subjects under...
OBJECTIVE: The purpose of this study is to evaluate the pharmacokinetics (PK) parameters of an ezetimibe 10 mg (test drug) and assess its bioequivalence to the branded reference product in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: A single-center, randomized, open-label, four-period, two-sequence, full replicate crossover study was conducted in 88 healthy Chinese subjects under fasting or fed conditions. Subjects received a single oral dose of 10 mg ezetimibe tablet as test or reference formulation. There was a minimum 14-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of free ezetimibe and total ezetimibe (ezetimibe + ezetimibe glucuronide) was determined by a validated ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Pharmacokinetik and bioavailability parameters were estimated via non-compartmental methods. Adverse events were also recorded. RESULTS: 40 and 48 eligible healthy subjects were enrolled in the fasted and fed study. Under fasting state, total ezetimibe with 90% confidence intervals (CIs) of C, AUC, and AUC were 87.17% (81.99 - 92.66%), 95.98% (92.38-99.72%), and 96.04% (91.37 - 100.95%), respectively. Under fed state, total ezetimibe with 90% confidence intervals (CIs) of C, AUC, and AUC were 98.71% (90.11 - 108.13%), 98.32% (94.71 - 102.06%), and 97.90% (92.68 - 103.42%), respectively. The 90% CIs of the ratio of geometric means (GMRs) of C, AUC, AUC of the test and reference formulation in both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80 - 1.25. No severe adverse events were observed. CONCLUSION: The test and reference 10-mg ezetimibe tablets were bioequivalent under fasting and fed conditions in Chinese subjects. Both preparations showed good safety and tolerability.
Corrigendum for the article Int J Clin Pharmacol Ther 2024; 11: 525-533.
Ikura M, Nakamura T, Wada K … +6 more , Nagata R, Ueno T, Kawabata K, Yoshihara F, Watanabe T, Tsukamoto Y
Int J Clin Pharmacol Ther · 2024 Dec · PMID 39445388 · Publisher ↗
Abstract loading — click title to view on PubMed.
Voriconazole trough levels after switching from an intravenous to oral formulation in a patient with short bowel syndrome.
Ishida R, Yasu T, Hayakawa M … +1 more , Terayama Y
Int J Clin Pharmacol Ther · 2024 Dec · PMID 39445387 · Publisher ↗
Abstract loading — click title to view on PubMed.
Association between trough plasma voriconazole concentration and adverse drug reactions in elderly patients.
Hu X, Tang M, Tang L … +3 more , Liu X, Chen L, Zhou J
Int J Clin Pharmacol Ther · 2025 Jan · PMID 39411861 · Publisher ↗
OBJECTIVE: Only limited data are available on trough plasma voriconazole concentration in elderly patients. This study aimed to assess the association between voriconazole concentration and adverse drug reactions (ADR)....
OBJECTIVE: Only limited data are available on trough plasma voriconazole concentration in elderly patients. This study aimed to assess the association between voriconazole concentration and adverse drug reactions (ADR). MATERIALS AND METHODS: A retrospective analysis was conducted to investigate the correlation between voriconazole trough concentration and adverse reactions among elderly patients admitted between October 1, 2017, and September 30, 2020. RESULTS: In total 147 patients were included in this study, with 248 measurements of voriconazole concentrations available. ADR occurred in 75 patients after drug therapy, with liver injury showing the highest incidence (n = 37, 49.33%), followed by hypokalemia (n = 27, 36%), and neurological disorder (n = 20, 26.67%). 121 measurements (48.79%) in 82 patients (55.78%) showed that the monitored trough concentration did not match the occurrence of ADR, mainly including hyponatremia, hypokalemia, liver injury, and kidney injury. CONCLUSION: The accuracy of predicting the trough concentration of voriconazole as recommended by current guidelines for elderly patients might be limited. Consequently, it is advisable to establish a tailored treatment range of voriconazole concentration specifically catered to this patient demographic.
Positive effects of magnesium supplementation in metabolic syndrome.
Kisters S, Kisters K, Werner T … +6 more , Vormann J, Tokmak F, Westhoff T, Gröber U, Predel HG, Reuter H
Int J Clin Pharmacol Ther · 2024 Dec · PMID 39380547 · Publisher ↗
INTRODUCTION: Recent data show that magnesium supplementation decreases systolic and diastolic blood pressure values depending on the blood pressure levels and improves metabolic parameters in cardiovascular disease. MAT...
INTRODUCTION: Recent data show that magnesium supplementation decreases systolic and diastolic blood pressure values depending on the blood pressure levels and improves metabolic parameters in cardiovascular disease. MATERIALS AND METHODS: In this context, we conducted a prospective, randomized, double-blind study on serum and ionized magnesium, systolic and diastolic blood pressure values, interleukin-6, vitamin D, and metabolic profile in 27 patients (13 male/14 female, age: 60.2 ± 12.5 years) with metabolic syndrome. All patients received 400 mg of oral magnesium supplementation daily. Parameters were measured before and after 6 and 12 weeks of treatment. 27 patients served as controls without additional magnesium treatment (10 male/17 female, age: 64.6 ± 13.2 years). RESULTS: There was no significant change in serum magnesium after 6 and 12 weeks of magnesium supplementation and in controls. Ionized magnesium significantly increased from 0.56 ± 0.05 to up to 0.63 ± 0.08 mmol/L (mean ± SD) (p < 0.01). The ionized Ca/Mg ratio was significantly increased at baseline in about 32% of all patients; after 12 weeks of magnesium supplementation, the Ca/Mg ratio decreased significantly from 2.32 ± 0.22 to 2.04 ± 0.24 at the end of the study (mean ± SD, p < 0.05). In the magnesium-treated group, there was a significant decrease in systolic and diastolic blood pressure values after 12 weeks (systolic: 134.6 ± 6.8 to 126.3 ± 5.6 mmHg, diastolic: 84.1 ± 3.9 to 79.4 ± 1.6 mmHg) (mean ± SD) (p < 0.01). Additional magnesium supplementation decreased interleukin-6 values significantly from 4.94 ± 3.30 to 4.53 ± 6.89 pg/mL after 6 weeks to 3.01 ± 1.32 pg/mL after 12 weeks (mean ± SD) (p < 0.01). In the control group, interleukin-6 was 3.73 ± 4.36 pg/mL before the start of the supplementation, 4.87 ± 4.35 pg/mL after 6 weeks, and 4.41 ± 3.15 pg/mL after 12 weeks (means ± SD) (n.s.). In patients receiving magnesium supplementation, vitamin D levels significantly improved from 17.93 ± 8.96 to 24.41 ± 10.20 ng/mL (mean ± SD) (p < 0.05). HbA1c and serum cholesterol values improved under magnesium therapy, but the improvement did not reach significance. For statistical analysis, Mann-Whitney-U-Test was used. CONCLUSION: Using supplementation with 400 mg magnesium for 12 weeks in patients with metabolic syndrome, ionized magnesium concentrations significantly increased, while serum magnesium did not change significantly. Both systolic and diastolic blood pressure values decreased significantly in the magnesium-treated group. Magnesium supplementation also significantly decreased interleukin-6 levels and increased vitamin D in patients. HbA1c and cholesterol levels improved with magnesium supplementation, but the improvement did not reach significance. The anti-inflammatory effects of magnesium as well as anti-arteriosclerotic effects of magnesium therapy are beneficial for patients with metabolic syndrome at high risk of cardiovascular disease and mortality.
A disproportionality analysis of antipsychotic-induced hyperprolactinemia based on FDA adverse event reporting system.
Song M, Li D, Peng J … +3 more , Wang N, Zhang M, Ren XL
Int J Clin Pharmacol Ther · 2024 Dec · PMID 39380546 · Publisher ↗
OBJECTIVE: This study aims to compare the risks of different antipsychotics in causing hyperprolactinemia, taking into account the age, gender, and onset time. MATERIALS AND METHODS: We searched the FDA Adverse Event Rep...
OBJECTIVE: This study aims to compare the risks of different antipsychotics in causing hyperprolactinemia, taking into account the age, gender, and onset time. MATERIALS AND METHODS: We searched the FDA Adverse Event Reporting System (FAERS) from January 1, 2004, to March 31, 2022, for reports of hyperprolactinemia treated with antipsychotics. We evaluated the association between antipsychotics and the risk of hyperprolactinemia using reporting odds ratio (ROR) based on a disproportionality analysis. Moreover, information regarding age, gender, countries, and onset time was collected. RESULTS: We found 4,430 reports of antipsychotic-induced hyperprolactinemia involving 13 different antipsychotics. From highest to lowest ROR value, the top five antipsychotics were as follows: risperidone (ROR = 631.0611; 95% CI: 592.7329, 671.8677) > amisulpride (ROR = 59.4425; 95% CI: 19.0668, 185.317) > paliperidone (ROR = 31.9885, 95% CI: 27.912, 36.6604) > fluphenazine (ROR = 15.6026; 95% CI: 5.0236, 48.4595) > haloperidol (ROR = 14.3861; 95% CI: 11.173, 18.5231). Except for three drugs (risperidone, haloperidol, and amisulpride), women outnumbered men in cases of antipsychotic-induced hyperprolactinemia. The age range was 13 - 64 years old, with the most being 19 - 44 years old, followed by 45 - 64 years old, and there were fewer elderly patients. From longest to shortest, the median onset time of these antipsychotics was as follows: cariprazine (305 days) > risperidone (304 days) > quetiapine (276 days) > haloperidol (183 days) > ziprasidone (54 days) > lurasidone (44.5 days) > olanzapine (41 days) > asenapine (15.5 days) > paliperidone (15 days) > aripiprazole (12 days) > clozapine (6 days). CONCLUSION: Risperidone had the greatest risk of increasing prolactin, whereas clozapine had the lowest. Antipsychotic-induced hyperprolactinemia was more common in women and middle-aged patients. Clozapine had the shortest onset time in raising prolactin, whereas cariprazine had the longest.
Skin adhesion of a newly developed, bioequivalent rotigotine patch formulation in comparison to the originator product: Results of a multi-center, randomized, crossover trial in patients with Parkinson's disease.
Jost WH, Wang M, Wauer G … +6 more , Dax A, Wedemeyer RS, Schug B, Warnke A, Leblanc A, Schurad B
Int J Clin Pharmacol Ther · 2025 Feb · PMID 39370808 · Publisher ↗
OBJECTIVES: To demonstrate adequate skin adhesion of a new once-daily rotigotine transdermal patch (ROT-TDS) compared to the originator product (reference) in patients with Parkinson's disease (PD). MATERIALS AND METHODS...
OBJECTIVES: To demonstrate adequate skin adhesion of a new once-daily rotigotine transdermal patch (ROT-TDS) compared to the originator product (reference) in patients with Parkinson's disease (PD). MATERIALS AND METHODS: Pharmacokinetic bioequivalence (PK BE) was assessed with the 4 mg/24h patches in healthy adults in a single-/multiple-dose, crossover trial. The trial investigating skin adhesion in PD patients (stable dose ≥ 8 mg/day rotigotine) was performed with the 8 mg/24h patches as a multiple-dose, crossover trial (4 alternating once-daily patch applications). Skin status (seborrhea, sweating) was characterized at screening. Adhesion was assessed 5 minutes after application and 5 minutes before removal of each patch. Systemic safety and skin irritation/sensitization were monitored. RESULTS: ROT-TDS was bioequivalent to the reference product in the PK BE trial in 48 randomized healthy subjects. In the skin adhesion trial in 43 randomized PD patients, the cumulative mean percentage of adhesion (90% CI) at the end-of-dosing interval was 92.948% (90.156 - 95.740%) for ROT-TDS and 90.471% (87.574 - 93.367%) for the reference. For ROT-TDS, 80.23% of patches were ≥ 90% adhered at the end-of-dosing interval, while this was the case for 67.44% of the reference patches. Safety and skin tolerability of both products were comparable; the most frequent treatment-related adverse event was application-site pruritus for both treatments at comparable extent. CONCLUSION: ROT-TDS - with shown BE to the originator reference product - displayed similar safety and local tolerability as the reference product in patients with PD. The results show a trend to improved skin adhesion of the new patch compared to the reference in the target population.
Identification of factors associated with vancomycin-induced acute kidney injury: A retrospective analysis using the Common Data Model.
Park SI, Kim JK, Yu U … +1 more , Park JI
Int J Clin Pharmacol Ther · 2024 Dec · PMID 39315482 · Publisher ↗
OBJECTIVE: Previous findings on predictors of vancomycin-induced acute kidney injury (AKI) are inconsistent. We aimed to identify the predictors of vancomycin-induced AKI using the Observational Medical Outcome Partnersh...
OBJECTIVE: Previous findings on predictors of vancomycin-induced acute kidney injury (AKI) are inconsistent. We aimed to identify the predictors of vancomycin-induced AKI using the Observational Medical Outcome Partnership Common Data Model. MATERIALS AND METHODS: We analyzed data from patients treated with vancomycin between January 1, 2012, and May 31, 2022, who were positive for and had undergone oxacillin susceptibility tests. After excluding patients without data for vancomycin or baseline serum creatinine levels, 116 patients were included in the final dataset. Data up to the third measured vancomycin concentration were collected for each patient. Logistic regression models were used to estimate the odds ratio and 95% confidence interval for each variable associated with vancomycin-induced AKI. RESULTS: High baseline serum creatinine levels, intensive care unit admission, and concurrent renal disorders were significantly associated with vancomycin-induced AKI. Although high trough levels or area under the curve values were not significantly associated with vancomycin-induced AKI, both were significantly higher in patients with AKI than in those without AKI at the second vancomycin concentration measurement. The proportion with trough levels > 20 mg/L was higher in patients with AKI than in those without AKI at the third measurement. CONCLUSION: Our findings revealed that underlying renal disease and intensive care unit admission are more significantly associated with vancomycin-induced AKI than vancomycin pharmacokinetic parameters or dosage, likely due to vancomycin concentration-based dosage adjustment in clinical settings. Our findings may help develop strategies for reducing the incidence of vancomycin-induced AKI; however, further prospective studies are essential.
Retrospective evaluation of medical information for predicting tazobactam/piperacillin-induced liver injury.
Amemiya T, Suzuki H
Int J Clin Pharmacol Ther · 2024 Dec · PMID 39315481 · Publisher ↗
OBJECTIVE: Tazobactam/piperacillin is a first-line treatment option for hospital-acquired pneumonia; however, drug-induced liver injury (DILI) is relatively frequently observed with tazobactam/piperacillin in clinical pr...
OBJECTIVE: Tazobactam/piperacillin is a first-line treatment option for hospital-acquired pneumonia; however, drug-induced liver injury (DILI) is relatively frequently observed with tazobactam/piperacillin in clinical practice. This study aimed to verify the usefulness of available patient data for predicting DILI prior to tazobactam/piperacillin administration. MATERIALS AND METHODS: Tazobactam/piperacillin-treated patients were retrospectively selected and divided into patients with and without DILI. Comparative analysis was performed regarding age, gender, dose, duration of treatment, clinical laboratory values prior to treatment initiation, and the types of organ-specific infections in both groups. RESULTS: Multiple logistic regression analyses indicated that elevated C-reactive protein (odds ratio (OR), 1.284; 95% confidence interval (CI), 1.172 - 1.406; p < 0.001) and high hemoglobin (OR, 1.697; 95% CI, 1.259 - 2.286; p < 0.001) levels prior to the administration of tazobactam/piperacillin were risk factors for DILI in males who received a 4.5-g dose. A predictive model for DILI risk was constructed by combining these test values and analyzed using receiver operating characteristic curves, obtaining 0.910 for the model construction set and 0.845 for the validation set. CONCLUSION: The development of DILI was predicted with good accuracy in males who received a 4.5-g dose with elevated C-reactive protein and hemoglobin.
Comparison of uric acid elevation between aspirin-ticagrelor and aspirin-clopidogrel during dual antiplatelet therapy.
Park S, Chi S, Yang JH … +2 more , Min M, Shin JY
Int J Clin Pharmacol Ther · 2024 Nov · PMID 39292013 · Publisher ↗
OBJECTIVE: This study investigated whether serum uric acid levels are more elevated in the aspirin-ticagrelor group than in the aspirin-clopidogrel group. Materials and Materials and methods: We conducted a retrospective...
OBJECTIVE: This study investigated whether serum uric acid levels are more elevated in the aspirin-ticagrelor group than in the aspirin-clopidogrel group. Materials and Materials and methods: We conducted a retrospective cohort study with patients between 2013 and 2020. Baseline and maximum serum uric acid levels within a 6-month follow-up period were analyzed to determine the increase in both groups. RESULTS: A total of 41,877 patients were enrolled. A statistically significant elevation of serum uric acid levels was found in the aspirin-ticagrelor group compared to the aspirin-clopidogrel group (odds ratio (OR; 95% confidence interval (CI)) = 1.36 (1.15 - 1.60), p < 0.001). Kidney dysfunction and diuretic use were also identified as risk factors for uric acid elevation. CONCLUSION: Monitoring serum uric acid levels is recommended during aspirin-ticagrelor therapy, especially in patients with kidney dysfunction or those using diuretics.
A case of a geriatric patient with thrombocytopenia after partial recovery from COVID-19.
Hayashi Y, Momo K, Ando M … +6 more , Koya H, Nagai T, Shinmura K, Tokimatsu I, Akutsu Y, Kurosawa M
Int J Clin Pharmacol Ther · 2024 Nov · PMID 39239685 · Publisher ↗
The global emergence of -COVID-19 has prompted rapid therapeutic and vaccine advancements; however, clinical evidence remains limited. With around a 50% fatality rate for COVID-19 patients with acute respiratory distress...
The global emergence of -COVID-19 has prompted rapid therapeutic and vaccine advancements; however, clinical evidence remains limited. With around a 50% fatality rate for COVID-19 patients with acute respiratory distress syndrome (ARDS), early intervention is crucial. This report details a severe case of post-COVID-19 thrombocytopenia in a 79-year-old man and emphasizes its critical nature. Despite negative initial COVID-19 test results, subsequent positive results led to treatment initiation, and severe thrombocytopenia persisted resulting in bleeding complications and death. Recognized as a hematological manifestation of COVID-19, thrombocytopenia in this geriatric patient highlights the need for extended post-COVID-19 monitoring and management. This underscores the importance of vigilance and timely intervention, especially in vulnerable populations, and emphasizes the need for further research to understand the intricate relationship between COVID-19 and thrombocytopenia.
Dosing strategy of tacrolimus when co-administered with tablet in renal transplant recipients.
Dai R, Cai Y, Li J … +5 more , Liu X, Fu Q, Huang M, Wang C, Chen P
Int J Clin Pharmacol Ther · 2024 Nov · PMID 39157918 · Publisher ↗
OBJECTIVE: Tacrolimus (TAC) is a first-line immunosuppressant to prevent allograft rejection. tablet is widely used as a TAC-sparing agent in China that could significantly elevate TAC exposure. However, insufficient da...
OBJECTIVE: Tacrolimus (TAC) is a first-line immunosuppressant to prevent allograft rejection. tablet is widely used as a TAC-sparing agent in China that could significantly elevate TAC exposure. However, insufficient data support the dose recommendation of TAC when co-administered with . MATERIALS AND METHODS: A total of 305 adult renal transplant patients with 2,541 TAC trough concentrations (C) were enrolled for population pharmacokinetic (PPK) modeling. polymorphism was genotyped, and corresponding clinical factors were recorded. Nonlinear mixed-effects modeling and Monte Carlo simulation were used for dose recommendation. PK parameters were calculated based on one-compartment model with first-order absorption and elimination. RESULTS: The estimated total clearance (CL/F) and volume of distribution (V/F) of TAC were 23.84 L/h and 1,075.96 L, respectively. , genotype, hematocrit (HCT), and weight were found to have a significant influence on CL/F. CL/F was significantly lower in the individuals who were non-expressers and received TAC together with . genotype (expressers or non-expressers), body weight (40 - 80 kg), and hematocrit (20 - 40%) were selected as the specific clinical scenarios, and the starting dose of TAC ranged from 1.5 to 4.5 mg when co-administered with . CONCLUSION: We establish a TAC PPK model comprising as a covariate in renal transplant recipients and recommend an initial dose of TAC when co-administered with , which could provide reference for the individualized regimens of TAC.
Bioequivalence study of two formulations of afatinib dimaleate tablets in healthy subjects under fasting conditions: A randomized, open-label, single-dose, crossover trial.
Liu Y, Lü L, Xu M … +7 more , Tao J, Ning Y, Shi Y, Dong Y, Cao Q, Ma J, Qiu Y
Int J Clin Pharmacol Ther · 2024 Oct · PMID 39157917 · Publisher ↗
OBJECTIVE: To evaluate the bioequivalence of two different afatinib dimaleate formulations in healthy Chinese subjects under fasting conditions and to assess their pharmacokinetic and safety profiles. MATERIALS AND METHO...
OBJECTIVE: To evaluate the bioequivalence of two different afatinib dimaleate formulations in healthy Chinese subjects under fasting conditions and to assess their pharmacokinetic and safety profiles. MATERIALS AND METHODS: This randomized, open-label, 2-period, crossover, bioequivalence study included 32 healthy Chinese subjects. The subjects were assigned to receive a single 40-mg dose of generic or brand-named afatinib dimaleate tablet. Blood samples were collected pre-dose and up to 120 hours after dosing. Healthy subjects orally took the trial preparation (T) (afatinib maleate tablets developed by Jiangxi Shanxiang Pharmaceutical Co., Ltd., Gan Zhou, China) and the reference preparation (R) (afatinib maleate tablets developed by Boehringer Ingelheim Pharma GmbH & Co., Ingelheim, Germany) under fasting conditions in the appropriate period according to the randomization. We measured the blood concentrations, calculated the pharmacokinetic parameters of the two preparations in the human body, and evaluated whether formulations were bioequivalent. Safety of the preparations in healthy subjects was monitored during the whole trial. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, i.e., from the time the subject received the test drug to the end of the last visit. RESULTS: Under fasting conditions, the 90% confidence intervals (CIs) of the geometric mean ratios of the test/reference for afatinib dimaleate were 93.34 - 103.92% for AUC, 90.26 - 105.52% for C, and 93.49 - 104.05% for AUC. CONCLUSION: The 90% CI for the geometric mean ratios (test/reference) of C, AUC, and AUC were within the range of 80.00 - 125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under fasting conditions. Both products were similar in terms of safety.
Pulmonary fibrosis insights and therapy targets from disease models and administration of the lipophilic diterpene, sodium tanshinone IIA sulfonate: Review and meta-analysis.
Peng LY, Shi JJ, Liang Y … +5 more , Li Y, Tang Y, Kai T, Yang A, Xiong ZY
Int J Clin Pharmacol Ther · 2024 Oct · PMID 39120081 · Publisher ↗
Pulmonary fibrosis (PF) is a chronic and progressive pulmonary interstitial disease of unknown etiology and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Seven databases were systemat...
Pulmonary fibrosis (PF) is a chronic and progressive pulmonary interstitial disease of unknown etiology and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Seven databases were systematically searched to evaluate the preclinical evidence of Tanshinone IIA (Tan IIA) on PF. The quality of the included studies was assessed using a 10-item risk of bias tool, and data were analyzed using RevMan 5.3 software. 22 experiments from 12 studies on a total of 248 animals were included. The results showed that PF phenotype, such as fibrotic score, collagen I (Col-I), collagen III (Col-III), hydroxyproline (Hyp), in the group treated with Tan IIA were significantly lower than those in the model group (p < 0.00001). The potential mechanisms of Tan IIA improvement of PF involve reducing inflammation, antioxidation, and suppressing activation of transforming growth factor beta 1 (TGF-β1). The subgroup analysis of different models, different rat species, and different dosage time showed significant reduction in fibrotic scores and Hyp levels with Tan IIA. The preclinical evidence indicated that Tan IIA might be a potent and promising agent for PF, but this conclusion should be further confirmed with more research.
Early acute kidney injury after tacrolimus administration in heart transplant recipients receiving basiliximab induction therapy.
Ikura M, Nakamura T, Wada K … +6 more , Nagata R, Ueno T, Kawabata K, Yoshihara F, Watanabe T, Tsukamoto Y
Int J Clin Pharmacol Ther · 2024 Nov · PMID 39120080 · Publisher ↗
OBJECTIVE: In this study, we aimed to analyze the association among the timing of tacrolimus initiation, time required to reach the target blood concentration, and early acute kidney injury (AKI) after tacrolimus adminis...
OBJECTIVE: In this study, we aimed to analyze the association among the timing of tacrolimus initiation, time required to reach the target blood concentration, and early acute kidney injury (AKI) after tacrolimus administration in heart transplant recipients who received basiliximab induction therapy. MATERIALS AND METHODS: 88 patients treated with tacrolimus-based immunosuppressive therapy were retrospectively reviewed. Induction therapy was administered to 52 patients. AKI was evaluated within 7 days of tacrolimus administration. RESULTS: The rate of increase in tacrolimus trough concentration to the target trough concentration of 10 µg/mL early after its administration was set to be similar in the basiliximab induction and non-induction group; 8 and 2 patients developed AKI in the induction and non-induction group, respectively. In the induction group, there was no significant difference in the timing of tacrolimus initiation and the time required to reach the target concentration between patients who developed and did not develop AKI. In contrast, the cumulative incidence of AKI was significantly different between patients with an estimated glomerular filtration rate below and those with an estimated glomerular filtration rate above 43 mL/min/1.73m at the start of tacrolimus administration (37.5% and 11.4%, respectively; p = 0.045). CONCLUSION: In patients receiving basiliximab induction therapy, the timing of tacrolimus initiation and the time to reach the target concentration are unlikely to be associated with early AKI after tacrolimus administration. However, the recovery of sufficient renal function after heart transplantation is important for determining the start time of tacrolimus.
Evaluation of metronidazole oral monotherapy in anaerobic oral infections.
Dar-Odeh N, Atef A, Flaifl Y … +4 more , Bobamuratova D, Akily B, Meer R, Abu-Hammad O
Int J Clin Pharmacol Ther · 2024 Nov · PMID 39120079 · Publisher ↗
OBJECTIVES: To evaluate the indications and dosing regimens for oral metronidazole monotherapy (OMM) for the management of oral anaerobic infections (OAIs) other than periodontitis. MATERIALS AND METHODS: The study follo...
OBJECTIVES: To evaluate the indications and dosing regimens for oral metronidazole monotherapy (OMM) for the management of oral anaerobic infections (OAIs) other than periodontitis. MATERIALS AND METHODS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in literature of PubMed/Medline, Scopus, and Cochrane databases. Data were retrieved from reports published in English in the period January 1, 1980 - August 30, 2023. Joanna Briggs Institute Critical Appraisal Tools were used to assess study risk of bias. RESULTS: A total of 228 articles were retrieved from the databases of which 16 met the inclusion criteria necessary for achieving the aims of the study. OAIs in which OMM was used or recommended included pericoronitis; necrotizing ulcerative gingivitis/periodontitis/stomatitis, osteomyelitis, acute periapical infection, and cellulitis. OMM was prescribed in dosages ranging from 200 to 500 mg t.i.d. for periods ranging from 2 to 7 days. Osteomyelitis of the jaw was the only infection for which the dosage regimen of metronidazole was not clearly described. CONCLUSION: Evidence from the databases searched support the view that OMM has clinical efficacy in the treatment of specific OAIs namely pericoronitis and necrotizing oral infections in immune-competent and immune-compromised patients. The evidence does not support the use of OMM in "deep tissue" infections such as osteomyelitis, and odontogenic infections such as acute apical infection and cellulitis. Clinical trials are warranted to determine the efficacy of OMM in comparison with other antibiotic regimens.
Post-marketing safety concerns with montelukast: A pharmacovigilance study based on the FDA adverse event reporting system.
Ou Z, Han Y, Zhuang W … +3 more , Xiao Y, Cai S, Zhang X
Int J Clin Pharmacol Ther · 2024 Nov · PMID 39099387 · Publisher ↗
The United States Food and Drug Administration (FDA) has been warning about the psychiatric disorders associated with montelukast (MTK) for years. To study the characteristics of the presence of MTK-associated adverse ev...
The United States Food and Drug Administration (FDA) has been warning about the psychiatric disorders associated with montelukast (MTK) for years. To study the characteristics of the presence of MTK-associated adverse events (AEs), we obtained data from the FDA Adverse Event Reporting System database and used a case (MTK) vs. non-case (all other drugs) analysis to investigate the safety signals in a disproportionality study. 27,507 reported AEs from January 2004 to December 2022 were analyzed. Disproportionality analysis shows that psychiatric, respiratory, thoracic, and mediastinal disorders as well as social circumstances are the most commonly reported AEs. In addition, our study found several unreported AEs, such as increased systolic blood pressure, diastolic dysfunction, hypothyroidism, obesity, bursitis, and polycystic ovaries. The timing of AE occurrence indicates that MTK-associated AEs are mainly acute effects. Most importantly, we found that 60.1% of patients reporting AEs in the category of psychiatric disorders were younger than 18 years. In summary, we revealed an age-preference pattern of psychiatric AEs in patients prescribed MTK. Our study is helpful for physicians and health professionals to better evaluate the value and risk of MTK and to achieve the goal of optimal patient care.
Pharmacokinetic, bioequivalence, and safety assessments of two brands of 30-mg nifedipine controlled-release formulations in Chinese healthy subjects.
Lu H, Zhou F, Rui C … +6 more , You H, Zhang W, Zhang Y, Ding J, Zhao S, Wu Q
Int J Clin Pharmacol Ther · 2024 Oct · PMID 39078055 · Publisher ↗
OBJECTIVE: This study aimed to analyze the pharmacokinetic (PK) characteristics, safety, and bioequivalence (BE) of a test (T) preparation of a nifedipine controlled-release tablet and the reference (R) drug (Adalat GTIS...
OBJECTIVE: This study aimed to analyze the pharmacokinetic (PK) characteristics, safety, and bioequivalence (BE) of a test (T) preparation of a nifedipine controlled-release tablet and the reference (R) drug (Adalat GTIS) in Chinese study participants in the context of fasting and postprandial states. MATERIALS AND METHODS: An open-label, single-center, randomized, single-dose, two-period study was designed including two separate arms, one with administration under fasting conditions and one with administration under postprandial conditions (high-fat, high-calorie breakfast). After oral administration, the nifedipine concentrations in plasma were quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) at regular intervals. Primary PK parameters, including the area under the concentration curve from 0 to infinity (AUC), the area under the concentration profile from 0 to the last measurable concentration time (AUC), and maximal measured plasma concentration (C) were log-transformed with BE limits of 80 - 125% to evaluate BE. All adverse events (AEs) were wholly supervised. RESULTS: The PK profiles of the T and R formulations were comparable to each other under both fasting and postprandial conditions. The 90% confidence intervals (CIs) of the AUC, AUC, and C were 92.69 - 106.06%, 93.32 - 107.05%, and 99.53 - 116.71%, respectively, under the fasting state. The 90% CIs of the AUC, AUC, and C were 105.05 - 117.40%, 105.43 - 117.82%, and 102.66 - 116.30%, respectively, in the postprandial arm. 47 cases of drug-associated AEs were noted in the entire research. CONCLUSION: Under both the fasting and postprandial states, the two nifedipine controlled-release formulations were bioequivalent and safe in healthy Chinese subjects.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe