Single-dose pharmacokinetic studies of abiraterone acetate in men with hepatic or renal impairment

J Clin Pharmacol. 2014 Jul;54(7):732-41. doi: 10.1002/jcph.253. Epub 2014 Jan 17.

Abstract

Three open-label, single-dose studies investigated the impact of hepatic or renal impairment on abiraterone acetate pharmacokinetics and safety/tolerability in non-cancer patients. Patients (n = 8 each group) with mild/moderate hepatic impairment or end-stage renal disease (ESRD), and age-, BMI-matched healthy controls received a single oral 1,000 mg abiraterone acetate (tablet dose); while patients (n = 8 each) with severe hepatic impairment and matched healthy controls received 125- and 2,000-mg abiraterone acetate (suspension doses), respectively (systemic exposure of abiraterone acetate suspension is approximately half to that of tablet formulation). Blood was sampled at specified timepoints up to 72 or 96 hours postdose to measure plasma abiraterone concentrations. Abiraterone exposure was comparable between healthy controls and patients with mild hepatic impairment or ESRD, but increased by 4-fold in patients with moderate hepatic impairment. Despite a 16-fold reduction in dose, abiraterone exposure in patients with severe hepatic impairment was about 22% and 44% of the Cmax and AUC∞ of healthy controls, respectively. These results suggest that abiraterone pharmacokinetics were not changed markedly in patients with ESRD or mild hepatic impairment. However, the capacity to eliminate abiraterone was substantially compromised in patients with moderate or severe hepatic impairment. A single-dose administration of abiraterone acetate was well-tolerated.

Trial registration: ClinicalTrials.gov NCT01516047 NCT01715259 NCT02001571.

Keywords: abiraterone acetate; hepatic impairment; pharmacokinetics; phase-I; renal impairment.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abiraterone Acetate
  • Adult
  • Aged
  • Aged, 80 and over
  • Androstadienes / administration & dosage
  • Androstadienes / adverse effects
  • Androstadienes / blood
  • Androstadienes / pharmacokinetics*
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / blood
  • Antineoplastic Agents, Hormonal / pharmacokinetics
  • Cytochrome P-450 Enzyme Inhibitors / administration & dosage
  • Cytochrome P-450 Enzyme Inhibitors / adverse effects
  • Cytochrome P-450 Enzyme Inhibitors / blood
  • Cytochrome P-450 Enzyme Inhibitors / pharmacokinetics*
  • Half-Life
  • Hepatic Insufficiency / blood
  • Hepatic Insufficiency / metabolism*
  • Hepatic Insufficiency / physiopathology
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / physiopathology
  • Male
  • Middle Aged
  • Prodrugs / administration & dosage
  • Prodrugs / adverse effects
  • Prodrugs / analysis
  • Prodrugs / pharmacokinetics*
  • Renal Dialysis / adverse effects
  • Renal Elimination
  • Renal Insufficiency / blood
  • Renal Insufficiency / metabolism*
  • Renal Insufficiency / physiopathology
  • Severity of Illness Index
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors
  • Steroid 17-alpha-Hydroxylase / metabolism
  • Suspensions
  • Tablets

Substances

  • Androstadienes
  • Antineoplastic Agents, Hormonal
  • Cytochrome P-450 Enzyme Inhibitors
  • Prodrugs
  • Suspensions
  • Tablets
  • Steroid 17-alpha-Hydroxylase
  • Abiraterone Acetate

Associated data

  • ClinicalTrials.gov/NCT01516047
  • ClinicalTrials.gov/NCT01715259
  • ClinicalTrials.gov/NCT02001571