title: Population pharmacokinetics and safety of eptifibatide in healthy Chinese volunteers and simulations on the dose regimens approved for a Western population.
abstract: OBJECTIVE
  This study was designed to evaluate the pharmacokinetics (PK) and safety of eptifibatide in healthy Chinese volunteers and provide information for the further study in the Chinese population.
  
  
  METHODS
  30 healthy volunteers (15 male) were enrolled in the study and divided into three dose groups (45 µg x kg⁻¹, 90 µg x kg⁻¹, and 180 µg x kg⁻¹). Plasma and urine samples were drawn after one single-bolus administration and measured by LC-MS/MS. The plasma and urine data were analyzed simultaneously by the population approach using the NONMEM software and evaluated by the visual predicted check (VPC) and bootstraping. The PK profiles of dose regimens approved for a Western population in the Chinese population were simulated.
  
  
  RESULTS
  A two-compartment model adequately described the PK profiles of eptifibatide. The clearance (CL) and the distribution volume (V₁) of the central compartment were 0.128 L x h⁻¹ x kg⁻¹ and 0.175 L x kg⁻¹, respectively. The clearance (Q) and V₂of the peripheral compartment were 0.0988 L x h⁻¹ x kg⁻¹ and 0.147 L x kg⁻¹, respectively. The elimination fraction from plasma to urine (F₀) was 17.2%. No covariates were found to have a significant effect. Inter-individual variabilites were all within 33.9%. The VPC plots and bootstrap results indicated good precision and prediction of the model. The simulations of the approved regimens in the Chinese population showed much lower steady-state concentrations than the target concentration obtained from the Western clinical trials. No severe safety events were found in this study.
  
  
  CONCLUSIONS
  The PK model of eptifibatide was established and could provide PK information for further studies in the Chinese population.
authors.forename: Xi-Pei
authors.initials: XP
authors.lastname: Wang
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Mai
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Zheng
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: He
authors.forename: Yue-Heng
authors.initials: YH
authors.lastname: Wu
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Shan
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D002681:China; D002853:Chromatography, Liquid; D003198:Computer Simulation; D054796:Drug Dosage Calculations; D000077542:Eptifibatide; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D061214:Patient Safety; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018570:Risk Assessment; D012984:Software; D053719:Tandem Mass Spectrometry; D019366:Western World; D044465:White People; D055815:Young Adult
chemical_list: D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D000077542:Eptifibatide