British journal of clinical pharmacology
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Br J Clin Pharmacol · Sep 2019
Randomized Controlled Trial Multicenter StudyEffects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite.
Quizartinib is an oral, highly potent and selective next-generation FMS-like tyrosine kinase 3 (FLT3) inhibitor under investigation in patients with FLT3-internal tandem duplication-mutated acute myeloid leukaemia. This drug-drug interaction study assessed the pharmacokinetics (PK) of quizartinib when coadministered with strong or moderate cytochrome P450 3A (CYP3A) inhibitors. ⋯ These results suggest reducing the dose of quizartinib when coadministered with a strong CYP3A inhibitor, but not with a moderate or weak CYP3A inhibitor. This dose reduction was implemented in phase 3 evaluation of quizartinib.
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Br J Clin Pharmacol · Sep 2019
Multicenter StudyOptimal route for administering tranexamic acid in primary unilateral total hip arthroplasty: Results from a multicenter cohort study.
This study aimed to compare the efficacy and safety of different tranexamic acid (TXA) routes following primary total hip arthroplasty (THA). ⋯ TXA is effective and safe to decrease blood loss and transfusion following primary THA, regardless of whether it is administered intravenously, topically or both. Intravenous or combined routes may produce better haemostatic effects, so they may be suggested in the absence of contraindications.
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Br J Clin Pharmacol · Mar 2019
Randomized Controlled Trial Multicenter StudyEffect of inotuzumab ozogamicin on the QT interval in patients with haematologic malignancies using QTc-concentration modelling.
The aim of this study was to characterize the effect of inotuzumab ozogamicin on QT interval in patients with B-cell malignancies. ⋯ Inotuzumab ozogamicin (1.8 mg m-2 per cycle) is not predicted to pose a clinically significant safety risk for QT prolongation in patients with acute lymphoblastic leukaemia or non-Hodgkin lymphoma.
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Br J Clin Pharmacol · Jan 2019
Multicenter StudyPopulation pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.
Carboplatin dosage is calculated by using the estimated glomerular filtration rate (GFR) to achieve a target plasma area under the plasma concentration-time curve (AUC). The aims of the present study were to investigate factors that influence the pharmacokinetics of carboplatin in children with high-risk neuroblastoma, and whether target exposures for carboplatin were achieved using current treatment protocols. ⋯ GFR did not appear to influence the pharmacokinetics of carboplatin after adjusting pharmacokinetic parameters for weight. This model-based approach validates the use of weight-based dosing as an appropriate alternative for carboplatin in children with either mild renal impairment or normal renal function.
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Br J Clin Pharmacol · Jun 2018
Randomized Controlled Trial Multicenter StudyExposure-response characterization of tofacitinib efficacy in moderate to severe ulcerative colitis: Results from a dose-ranging phase 2 trial.
Tofacitinib is an oral, small molecule JAK inhibitor being investigated for ulcerative colitis (UC). In a phase 2 dose-ranging study, tofacitinib demonstrated efficacy vs. placebo as UC induction therapy. In this posthoc analysis, we aimed to compare tofacitinib dose and plasma concentration as predictors of efficacy and identify covariates that determined efficacy in patients with UC. ⋯ Exposure-response characterization demonstrated the potential of tofacitinib 10 and 15 mg twice daily as induction therapy for UC without monitoring of plasma drug concentrations for dose optimization.