Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients.
Article Details
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Ohno T, Nakade S, Nakayama K, Kitagawa J, Miyabe H, Konomi T, Miyata Y
Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients.
Drug Metab Pharmacokinet. 2008;23(6):456-63.
- PubMed ID
- 19122340 [ View in PubMed]
- Abstract
The objectives of this study were to develop a population pharmacokinetic model of imidafenacin and to explore the factors that affect the pharmacokinetics of imidafenecin. A total of 2406 plasma samples were collected from 90 healthy volunteers and 457 patients with overactive bladder. We determined the plasma concentrations of imidafenacin by liquid chromatography with tandem mass spectrometry; resultant data were analyzed by a population approach using NONMEM software. The imidafenacin plasma concentration time course was described using a two-compartment model with first-order absorption and lag time. The robustness of the population pharmacokinetic model was evaluated by bootstrap resampling. The results of the population pharmacokinetic analysis demonstrated that oral clearance was decreased with advancing age, increasing hepatic function parameters (AST and ALP), food intake, and itraconazole coadministration, while the first-order absorption rate constant was decreased with food intake. All parameter estimates from the final model fell within 20% of the bootstrapped mean. In conclusion, we developed a population pharmacokinetic model for imidafenacin that well-described plasma concentration profiles. We also identified the factors affecting imidafenacin pharmacokinetics.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Imidafenacin Cytochrome P450 3A4 Protein Humans NoSubstrateDetails Imidafenacin UDP-glucuronosyltransferase 1-4 Protein Humans NoSubstrateDetails - Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Imidafenacin alpha1-acid glycoprotein (Protein Group) Protein group Humans NoSubstrateDetails Imidafenacin Serum albumin Protein Humans NoSubstrateDetails