PHARMACOKINETICS, DISPOSITION AND BIOTRANSFORMATION OF [C-14] RADIOLABELED VALSARTAN IN HEALTHY MALE-VOLUNTEERS AFTER A SINGLE ORAL DOSE

1. The disposition of valsartan, a potent angiotensin II receptor anta gonist, was investigated in six healthy male volunteers. They each rec eived a single oral dose of 80 mg of a C-14-labelled preparation as a neutral buffered solution. 2. Peak concentrations of radioactivity and valsartan in plasma measured Ih after dosing showed rapid onset of ab sorption. 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 valsar tan and radioactivity was fast and multiexponential. beta-Half-lives o f 6 +/- 1 h were observed. In a terminal elimination phase, low radioa ctivity levels decreased with a half-life of 81 +/- 33 h. A minor, pha rmacologically inactive metabolite (valeryl-4-hydroxy-valsartan; M1) w as detected in the plasma at rime points later than 2 h after dosing, representing approximately 11% of the AUC((24 h)) of plasma radioactiv ity. 4. The bulk of the dose was excreted within 4 days. The total exc retion within 7 days amounted to 99 +/- 1% of dose. Faecal excretion w as predominant (86 +/- 5% of dose). Valsartan was largely excreted unc hanged (81 +/- 5% of the dose in the excreta). The predominant clearan ce mechanism appeared to be direct elimination via bile. 5. An inactiv e metabolite, M1, was formed by oxidative biotransformation and accoun ted for 9 +/- 3% of the dose in the excreta.