Steady‐state pharmacokinetics of sirolimus in stable adult Chinese renal transplant patients. Issue 3 (10th February 2014)

• Record Type: Journal Article
• Authors: Wang, Huifen Faye; Qiu, Feng; Wu, Xiongfe; Fang, Juanzhi; Crownover, Penelope; Korth‐Bradley, Joan; Schulman, Seth
• Is Part Of: Clinical pharmacology in drug development. Volume 3:Issue 3(2014:May/Jun.)
• Page Start: 235
• Page End: 241
• Publication Date: 2014-02-10
• Subjects: Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.96
• Languages: English
• ISSNs: 2160-7648

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="cpdd96-sec-0001" sec-type="section"> <p>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 (C<sub>max</sub>), area under the concentration–time curve within a dosing interval of τ (AUC<sub>τ</sub>), oral clearance (CL/F), and trough concentration (C<sub>trough</sub>) 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 t<sub>max</sub> (range) was 2.49 hours (1–12 hours). A strong correlation was observed between C<sub>trough</sub> and AUC<sub>τ</sub>. 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.</p> </sec> </abstract>