A Semi-Mechanistic Population Pharmacokinetic Model of Noscapine in Healthy Subjects Considering Hepatic First-Pass Extraction and CYP2C9 Genotypes

Autor: Zhendong Chen, Max Taubert, Chunli Chen, Jana Boland, Qian Dong, Muhammad Bilal, Charalambos Dokos, Bertil Wachall, Manfred Wargenau, Bernhard Scheidel, Martin H. J. Wiesen, Elke Schaeffeler, Roman Tremmel, Matthias Schwab, Uwe Fuhr
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Drugs in R&D, Vol 24, Iss 2, Pp 187-199 (2024)
Druh dokumentu: article
ISSN: 1174-5886
1179-6901
DOI: 10.1007/s40268-024-00466-6
Popis: Abstract Introduction Noscapine is a commonly used cough suppressant, with ongoing research on its anti-inflammatory and anti-tumor properties. The drug has a pronounced pharmacokinetic variability. Objective This evaluation aims to describe the pharmacokinetics of noscapine using a semi-mechanistic population pharmacokinetic model and to identify covariates that could explain inter-individual pharmacokinetic variability. Methods Forty-eight healthy volunteers (30 men and 18 women, mean age 33 years) were enrolled in a randomized, two-period, two-stage, crossover bioequivalence study of noscapine in two different liquid formulations. Noscapine plasma concentrations following oral administration of noscapine 50 mg were evaluated by a non-compartmental analysis and by a population pharmacokinetic model separately. Results Compared to the reference formulation, the test formulation exhibited ratios (with 94.12% confidence intervals) of 0.784 (0.662–0.929) and 0.827 (0.762–0.925) for peak plasma concentrations and area under the plasma concentration–time curve, respectively. Significant differences in p values (
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