title: Comparative bioavailability and pharmacokinetics of sirolimus tablets in healthy Chinese volunteers.
abstract: OBJECTIVE
  Although sirolimus tablets and oral solutions have been used in clinical practice, no study has been reported on the pharmacokinetics and bioavailability of a single-dose of sirolimus tablets in healthy Chinese volunteers. The purpose of this study was to compare the bioavailability and pharmacokinetic (PK) properties of two different 1-mg sirolimus tablets in healthy Chinese male volunteers and evaluate whether a generic tablet of sirolimus meets the criteria for bioequivalence from the State Food and Drug Administration (SFDA) of China when compared with a reference product.
  
  
  METHODS
  A total of 24 healthy Chinese volunteers was eligible for this 6 mg single dose, randomized-sequence, open-label, 2-period crossover study. Blood samples were collected before dosing and at 0.25, 0.50, 0.75, 1.0, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 120, 168, 216, and 264 hours after dosing. Whole blood sirolimus concentration was analyzed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic properties of sirolimus were assessed using noncompartmental analysis.
  
  
  RESULTS
  The mean (range) Cmax values of the test and the reference were 15.25 (8.48 - 24.40) and 13.43 (7.90 - 22.90) ng/ml; AUC0-t values were 475.65 (293.33 - 1049.86) and 451.96 (221.52 - 809.11) ng/h/ml. The medians (range) tmax values were 2.0 (1.0 - 8.0) and 2.0 (1.0 - 8.0) hours, respectively. The 90% confidence intervals (CIs) for the ratios of Cmax, AUC0-264, and AUC0-∞ were 103.7% to 124.4%, 97.5% to 113.6%, and 98.0% to 114.8%, respectively.
  
  
  CONCLUSIONS
  In this single-dose crossover study the test sirolimus tablets met the criteria for bioequivalence in terms of both rate and extent. Each sirolimus formulation was well tolerated during the study.
authors.forename: Ming-zhu
authors.initials: MZ
authors.lastname: Huang
authors.forename: Jun-chun
authors.initials: JC
authors.lastname: Chen
authors.forename: Xing-jiang
authors.initials: XJ
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Guo-lan
authors.initials: GL
authors.lastname: Wu
authors.forename: Hui-li
authors.initials: HL
authors.lastname: Zhou
authors.forename: Mei-Xiang
authors.initials: MX
authors.lastname: Zhu
authors.forename: Li-hua
authors.initials: LH
authors.lastname: Wu
authors.forename: Jian-zhong
authors.initials: JZ
authors.lastname: Shen Tu
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000493:pharmacokinetics; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D020123:Sirolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
chemical_list: D016568:Drugs, Generic; D013607:Tablets; D020123:Sirolimus