Estimation of CYP2D6*10 genotypes on citalopram disposition in Chinese subjects by population pharmacokinetic assay
Estimation of CYP2D6*10 genotypes on citalopram disposition in Chinese subjects by population pharmacokinetic assay
There is great interindividual variability in citalopram (CIT) pharmacokinetics. We attempted to establish a population pharmacokinetic (PPK) model of CIT in Chinese healthy subjects, to evaluate the effect of genetic polymorphism on CIT pharmacokinetics and to compare the PPK and non-compartmental (NCA) assays in the estimation of CIT bioequivalence.Blood samples of 23 healthy subjects were collected after administration of CIT; plasma concentration of CIT was analysed using LC/MS-MS. CYP2C19 and CYP2D6*10 genotypes were determined. PPK model was established by using nonlinear mixed-effect modelling (NONMEM). The model was evaluated using goodness-of-fit plots and relative error measurements. Bioequivalence of CIT was evaluated by both PPK and NCA method.The estimated population absorption rate constant (ka ), clearance (CL/F) and volume of distribution (Vd/F) in Chinese healthy subjects are 0.64 L/h, 12.7 L/h and 705 L, respectively. Different CYP2C19 and CYP2D6 genotypes have impacts on CIT pharmacokinetics. There is about 5.5% decrement of CL/F for each CYP2C19*2 or CYP2D6*10 allele. The 90% confidence interval of CIT bioavailability obtained from NCA and PPK model were 96.4-105.4% and 92.5-103.4%, respectively.The PPK of CIT is best characterized by a one-compartment disposition model with first-order absorption. CYP2C19 and CYP2D6 genotypes have impacts on the CL/F of CIT. Bioequivalence of CIT can be estimated by both NCA and PPK model.
- University of Michigan United States
- University of Michigan–Ann Arbor United States
- University of Michigan–Flint United States
- Ruijin Hospital China (People's Republic of)
- Shanghai Jiao Tong University China (People's Republic of)
Adult, Male, Genotype, Chemistry, Pharmaceutical, Population, Citalopram, Young Adult, Asian People, Pharmacy and Pharmacology, Health Sciences, Humans, Non‐Compartment, Bioequivalence, Cross-Over Studies, Models, Statistical, Polymorphism, Genetic, Population Pharmacokinetic, Antidepressive Agents, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2D6, Therapeutic Equivalency, CYP 2 C 19, Aryl Hydrocarbon Hydroxylases, CYP 2 D 6
Adult, Male, Genotype, Chemistry, Pharmaceutical, Population, Citalopram, Young Adult, Asian People, Pharmacy and Pharmacology, Health Sciences, Humans, Non‐Compartment, Bioequivalence, Cross-Over Studies, Models, Statistical, Polymorphism, Genetic, Population Pharmacokinetic, Antidepressive Agents, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2D6, Therapeutic Equivalency, CYP 2 C 19, Aryl Hydrocarbon Hydroxylases, CYP 2 D 6
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