title: Effect of probenecid on pharmacokinetics and tolerability of olmesartan in healthy chinese volunteers.
abstract: BACKGROUND
  Olmesartan is an angiotensin II receptor antagonist and is effective and well tolerated in the treatment of arterial hypertension. Probenecid is a well-established hypouricemic agent for the treatment of hyperuricemia and gout.
  
  
  OBJECTIVE
  The goal of this study was to examine the impact of coadministration of probenecid on the pharmacokinetic parameters and tolerability of olmesartan in healthy volunteers.
  
  
  METHODS
  In a randomized, open-label, 2-way crossover study, 12 volunteers received 2 oral treatments (olmesartan alone or olmesartan plus probenecid) separated by 4 days. Blood samples were obtained for a 48-hour pharmacokinetic evaluation after drug administration. Tolerability was assessed by monitoring vital signs and laboratory tests before and after administration of the study drug.
  
  
  RESULTS
  Pharmacokinetic parameters were evaluated in 6 male and 6 female healthy volunteers (mean age, 22 [range, 20-25] years]; weight, 56.0 [range, 51.0-60.0] kg). Probenecid coadministration increased olmesartan Css-av, AUC0→∞, and AUC0-48 by 40%, 50%, and 50%, respectively (P = 0.018, 0.000, 0.000, respectively), but there was no statistical significance for Tmax, t1/2, Css-max, and Css-min between olmesartan plus probenecid and olmesartan alone (P = 0.697, 0.053, 0.521, and 0.734, respectively). No serious adverse event (AE) was reported during the study. The proportion of volunteers with AEs in the olmesartan plus probenecid period (5 of 12 [42%]) was higher than that in the olmesartan-alone period (1 of 12 [8%]). All of the AEs during the olmesartan plus probenecid period were abnormal routine urine test results. The AE in olmesartan-alone period was dizziness. All AEs were classified as mild and considered to be at least possibly related to treatment. All volunteers recovered from the AEs by 2 weeks after the end of the study.
  
  
  CONCLUSIONS
  Probenecid increases the exposure speed of olmesartan by increasing the AUC0-48, AUC0→∞, and Css-av. The combined treatment of olmesartan medoxomil with probenecid may increase the occurrence of genitourinary side effects. ClinicalTrials.gov identifier: NCT01907373.
authors: Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
authors: Kun-Yan
authors: KY
authors: Li
authors: Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
authors: Yu
authors: Y
authors: Qiu
authors: Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
authors: Yun
authors: Y
authors: Jiang
authors: Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
authors: Chen-Hui
authors: CH
authors: Luo
authors: Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
authors: Xiao-Ping
authors: XP
authors: Lin
authors: Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
authors: Jing
authors: J
authors: Wang
authors: Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
authors: Nong
authors: N
authors: Yang
keywords: olmesartan; pharmacokinetics; probenecid; tolerability