Pharmacokinetics, disposition and biotransformation of [14C]-radiolabelled valsartan in healthy male volunteers after a single oral dose

Xenobiotica. 1997 Jan;27(1):59-71. doi: 10.1080/004982597240767.

Abstract

1. The disposition of valsartan, a potent angiotensin II receptor antagonist, was investigated in six healthy male volunteers. They each received a single oral dose of 80 mg of a 14C-labelled preparation as a neutral buffered solution. 2. Peak concentrations of radioactivity and valsartan in plasma measured 1 h after dosing showed rapid onset of absorption. The results of this study combined with other available data indicate that at least 51% of the dose was absorbed. 3. Valsartan was the predominant radioactive compound in plasma. Elimination of valsartan and radioactivity was fast and multiexponential. beta-Half-lives of 6 +/- 1 h were observed. In a terminal elimination phase, low radioactivity levels decreased with a half-life of 81 +/- 33 h. A minor, pharmacologically inactive metabolite (valeryl-4-hydroxy-valsartan; M1) was detected in the plasma at time points later than 2 h after dosing, representing approximately 11% of the AUC(24 h) of plasma radioactivity. 4. The bulk of the dose was excreted within 4 days. The total excretion within 7 days amounted to 99 +/- 1% of dose. Faecal excretion was predominant (86 +/- 5% of dose). Valsartan was largely excreted unchanged (81 +/- 5% of the dose in the excreta). The predominant clearance mechanism appeared to be direct elimination via bile. 5. An inactive metabolite, M1, was formed by oxidative biotransformation and accounted for 9 +/- 3% of the dose in the excreta.

MeSH terms

  • Administration, Oral
  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / blood
  • Antihypertensive Agents / pharmacokinetics*
  • Antihypertensive Agents / urine
  • Biotransformation
  • Carbon Radioisotopes
  • Chromatography, High Pressure Liquid
  • Feces / chemistry
  • Fluorometry
  • Humans
  • Male
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin / drug effects
  • Tetrazoles / administration & dosage
  • Tetrazoles / blood
  • Tetrazoles / pharmacokinetics*
  • Tetrazoles / urine
  • Valine / administration & dosage
  • Valine / analogs & derivatives*
  • Valine / blood
  • Valine / pharmacokinetics
  • Valine / urine
  • Valsartan

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Carbon Radioisotopes
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin
  • Tetrazoles
  • Valsartan
  • Valine