title: Single- and multiple-dose pharmacokinetics and tolerability of limaprost in healthy Chinese subjects.
abstract: OBJECTIVE
  Limaprost, a prostaglandin E1 analogue, is used to treat various symptoms in patients with ischemic diseases. The present study was designed to determine the pharmacokinetics and tolerability of single and multiple oral doses of limaprost 5 μg tablets in healthy Chinese subjects.
  
  
  METHODS
  Single and multiple doses of 5-μg limaprost were orally administered to 12 healthy Chinese subjects. There was a 2-week washout period between single and multiple dosing. Blood samples were collected at various times. Indomethacin and aspirin were added to the blood samples to inhibit the endogenous release of prostaglandins during the sample processing. Plasma limaprost was measured by a two-dimensional liquid chromatography-tandem mass spectrometry method.
  
  
  RESULTS
  After single dosing, limaprost was rapidly absorbed (time to reach maximum plasma concentration [t max] = 22.50 min) and eliminated (elimination half-life [t ½] = 21.70 min), with the maximum plasma concentration (C max) being 2.56 pg/mL and area under the concentration-time curve (AUC) from time 0 to the last quantifiable time point (AUC0-t) being 70.68 pg·min/mL. There were significant inter-individual variations in the AUCs for both single- and multiple-dose regimens. The values of C max, AUC, t ½ and t max were not statistically different between single and multiple dosing. The accumulation factor R was 0.609 ± 0.432 (R < 1), indicating that there was no accumulation after multiple dosing. There were no statistically significant differences in pharmacokinetic parameters for both single and multiple dosing between female and male subjects. The drug was well tolerated, with no severe adverse events being observed.
  
  
  CONCLUSIONS
  Limaprost is rapidly absorbed after oral administration and is rapidly eliminated, with no accumulation after multiple dosing. The drug is well tolerated and no serious adverse events occurred.
authors.affiliation: Phase I Clinical Trial Unit, The First Hospital of Jilin University, China-Frontage USA, Jilin University, Xinmin Street, Changchun, Jilin, 130021, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanfu
authors.initials: Y
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.forename: Chengjiao
authors.initials: C
authors.lastname: Liu
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Cao
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000527:Alprostadil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002681:China; D004305:Dose-Response Relationship, Drug; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008968:Molecular Conformation; D013607:Tablets; D055815:Young Adult
chemical_list: D013607:Tablets; D000527:Alprostadil; C059238:limaprost