Steady-state pharmacokinetics of sirolimus in stable adult Chinese renal transplant patients
| Autor: | Huifen Faye, Wang, Feng, Qiu, Xiongfe, Wu, Juanzhi, Fang, Penelope, Crownover, Joan, Korth-Bradley, Seth, Schulman |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Sirolimus China Genotype Pharmacogenomic Variants Metabolic Clearance Rate Administration Oral Middle Aged Kidney Transplantation Models Biological Young Adult Phenotype Asian People Pharmacogenetics Tandem Mass Spectrometry Area Under Curve Cyclosporine Cytochrome P-450 CYP3A Humans Drug Therapy Combination Female Drug Monitoring Chromatography High Pressure Liquid Immunosuppressive Agents |
| Zdroj: | Clinical pharmacology in drug development. 3(3) |
| ISSN: | 2160-7648 |
| Popis: | This open-label, nonrandomized study was conducted to evaluate the steady-state pharmacokinetics of sirolimus in 24 stable Chinese renal transplant patients receiving daily oral maintenance doses of sirolimus (1-4 mg). Repeated trough and serial whole blood sirolimus concentrations over a 24-hour dosing interval were collected and assayed using high-performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS). Non-compartmental analysis (NCA) was employed to calculate sirolimus pharmacokinetic parameters. Cytochrome P450 (CYP) 3A5 genotyping was performed. Cyclosporine (CsA) levels were determined for patients who took concomitant CsA. Mean (±SD) sirolimus maximum concentration (Cmax ), area under the concentration-time curve within a dosing interval of τ (AUCτ ), oral clearance (CL/F), and trough concentration (Ctrough ) at steady state were: 14.1 ± 13.4 ng/mL, 199 ± 210 ng · h/mL, 10.1 ± 4.4 L/h, and 5.9 ± 6.3 ng/mL, respectively. Median tmax (range) was 2.49 hours (1-12 hours). A strong correlation was observed between Ctrough and AUCτ . Pharmacokinetics of sirolimus in patients with and without concomitant CsA were comparable. Allele frequency of CYP3A5*3 was 70.9% and a trend of higher oral clearance was observed in CYP3A5 expressers compared with non-expressers although the number of subjects in each genotype was small. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text