Pharmacokinetics of temocapril and temocaprilat after 14 once daily oral doses of temocapril in hypertensive patients with varying degrees of renal impairment

Br J Clin Pharmacol. 1997 Dec;44(6):531-6. doi: 10.1046/j.1365-2125.1997.t01-1-00622.x.

Abstract

Aims: The aim of this study was to determine the potential influence of renal impairment on the pharmacokinetics of temocapril and its pharmacologically active diacid metabolite, temocaprilat.

Methods: Non-compartmental pharmacokinetics were assessed in four groups of hypertensive patients (n=8 per group, four investigational centres) with normal (creatinine clearance determined via 24 h urine sampling, CL[CR], > or = 60 ml min-1) and impaired renal function (CL[CR] 40-59, 20-39, < 20 ml min-1) after 14 once daily oral doses of 10 mg temocapril hydrochloride.

Results: For temocapril, there were no statistically significant differences in median tmax or mean Cmax, AUC(SS), t1/2,Z, CL/F between the four groups. Renal clearance, CL(R), for temocapril showed a linear decreasing trend with decreasing CL(CR) [mean (s.d.): 32.2 (10.7) to 3.7 (3.0) ml min-1]. Steady-state for temocaprilat was reached on day 5. For temocaprilat, no statistically significant differences in mean Cmax or median tma were detected. With decreasing mean CL(CR), mean AUC(SS) for temocaprilat increased statistically significantly although only 2.4-fold [mean (s.d.): 2115 (565) to 4989 (2338) ng ml-1 h] and t1/2,Z was prolonged [mean (s.d.): 15.2 (1.2) to 20.0 (7.5) h]. CL(R) for temocaprilat showed a linear decreasing trend with decreasing CL(CR) [mean (s.d.): 20.2 (4.3) to 3.0 (1.8) ml min-1].

Conclusions: These results indicate that impaired renal function has only a limited effect on the pharmacokinetics of temocapril and its active metabolite, temocaprilat. This may be attributed to the dual, i.e. renal and biliary, elimination pathway of the drug.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics*
  • Area Under Curve
  • Creatinine / blood
  • Female
  • Humans
  • Kidney Diseases / metabolism*
  • Male
  • Middle Aged
  • Thiazepines / administration & dosage
  • Thiazepines / adverse effects
  • Thiazepines / pharmacokinetics*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Thiazepines
  • temocaprilat
  • temocapril hydrochloride
  • Creatinine