Clin Pharmacokinet
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Randomized Controlled Trial
Bayesian Population Model of the Pharmacokinetics of Venetoclax in Combination with Rituximab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Results from the Phase III MURANO Study.
Venetoclax is a selective B-cell lymphoma-2 (BCL-2) inhibitor approved for use as monotherapy or with rituximab in patients with chronic lymphocytic leukemia (CLL). The objectives of the current analysis of observed data from adult patients randomized to venetoclax-rituximab in the phase III MURANO study were to characterize venetoclax pharmacokinetics (PKs) using a Bayesian approach, evaluate whether a previously developed population PK model for venetoclax can describe the PKs of venetoclax when administered with rituximab, and to determine post hoc estimates of PK parameters for the exposure-response analysis. ⋯ The Bayesian model successfully characterized venetoclax PKs over time and confirmed key covariates affecting PKs in the MURANO study. The model was deemed appropriate for further use in simulations and for generating individual patient PK parameters for subsequent exposure-response evaluation.
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Randomized Controlled Trial Multicenter Study
Population Pharmacokinetics/Pharmacodynamics of Ticagrelor in Children with Sickle Cell Disease.
Ticagrelor, a reversible P2Y12 platelet inhibitor, is under investigation as a sickle cell disease (SCD) therapy in children. HESTIA1 (NCT02214121) was the first ticagrelor study generating pharmacokinetic (PK), pharmacodynamic (PD, P2Y12 reactivity units [PRU]), and safety data in 45 pediatric SCD patients. Population PK and PK/PD relationships for ticagrelor were quantified using a PK approach. ⋯ These analyses offer the first quantitative characterization of the dose-exposure-response relationship for ticagrelor in pediatric SCD patients. This model-based approach may be used to inform dose selection and design of subsequent studies that aim to define ticagrelor safety and efficacy in pediatric SCD patients.
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Randomized Controlled Trial Clinical Trial
Microdosed Cocktail of Three Oral Factor Xa Inhibitors to Evaluate Drug-Drug Interactions with Potential Perpetrator Drugs.
The aim of this study was to prove the suitability of simultaneously administered microdoses of the factor Xa inhibitors (FXaIs) rivaroxaban, apixaban and edoxaban (100 µg in total). To evaluate drug-drug interactions, the impact of ketoconazole, a known strong inhibitor of cytochrome P450 3A4 and P-glycoprotein, was studied. ⋯ EudraCT 2016-003024-23.
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Randomized Controlled Trial
Population-Pharmacokinetic Modeling of Tildrakizumab (MK-3222), an Anti-Interleukin-23-p19 Monoclonal Antibody, in Healthy Volunteers and Subjects with Psoriasis.
Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody recently approved for the treatment of chronic plaque psoriasis. ⋯ The pharmacokinetics of tildrakizumab behaves like a typical monoclonal antibody without requiring dosage adjustment.
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Randomized Controlled Trial Multicenter Study
Pharmacokinetics of the B-Cell Lymphoma 2 (Bcl-2) Inhibitor Venetoclax in Female Subjects with Systemic Lupus Erythematosus.
Venetoclax is an oral selective Bcl-2 inhibitor approved for the treatment of patients with chronic lymphocytic leukemia with 17p deletion. Mechanistic and preclinical evidence warranted evaluation of venetoclax for the treatment of systemic lupus erythematosus (SLE). This work characterized the pharmacokinetics of venetoclax in female subjects with SLE. ⋯ NCT01686555.