METABOLIC AND PHARMACOKINETIC STUDIES FOLLOWING ORAL-ADMINISTRATION OF C-14 FAMCICLOVIR TO HEALTHY-SUBJECTS

1. Following oral administration of C-14-famciclovir (500mg) to three healthy male subjects, drug-related material was rapidly absorbed as j udged by peak plasma concentrations of radioactive material being achi eved by 0.75h (6.7+/-0.9 mu g equiv./ml (mean i SD). 2. Famciclovir un derwent extensive first-pass metabolism and was only detected in the p lasma of one subject at low concentrations (0.5 mu g/ml). Famciclovir was rapidly and extensively metabolized to the active antiviral compou nd penciclovir, which reached peak concentrations in the plasma of 3.6 +/- 0.7 mu g/ml (0.75 h). The plasma elimination half-life value for penciclovir was 2.1 +/- 0.1h. The 6-deoxy precursor of penciclovir, BR L 42359, was the only other relatively major metabolite detected in pl asma. Peak plasma concentrations of BRL 42359 (1.0 +/- 0.1 mu g/ml) we re achieved at 0.5 h. 3. After 3 days, 73.0 +/- 6.1% of the radioactiv e dose was excreted in urine, showing that good absorption of drug-rel ated material occurred. Penal excretion was rapid since 60.2 +/- 4.2 a nd 72.3 +/- 5.7% of the dose was recovered in the urine samples collec ted up to 6 and 24 h, respectively. A good recovery of the administere d radioactive dose was obtained since a further 26.6 +/- 5.1% of the d ose was excreted in the faeces over a 72-h period. 4. Penciclovir and BRL 42359 were the major metabolites detected in urine and faeces. Pen ciclovir accounted for 59.2 +/- 4.9 and 4.2 +/- 1.4% of the dose in 0- 24 h urine and 0-48 h faeces, respectively. Corresponding values for B RL 42359 were 5.0 +/- 0.5 and 17.0 +/- 6.2%, respectively. These metab olites were identified in the biological samples using hplc-ms and ms- ms with thermospray ionization.