| pubmed-article:8893041 | pubmed:abstractText | 1. The pharmacokinetics of ranitidine were studied in the male beagle dog at a dose level of 50 mg (intravenous) or 5 mg/kg (oral). 2. After intravenous administration, Clp was moderate (10.4 ml/min/kg) with Clr accounting for approximately 30% of total clearance. Vdarea was 3.5 l/kg, resulting in a t1/2 of approximately 4 h. 3. After oral administration, F was good (73%) with peak plasma concentrations of ranitidine (2 micrograms/ml) achieved within 0.5-1 h hour after dosing. t1/2 (4.1 h) was similar to that observed after intravenous administration. 4. The absorption, metabolism and excretion of [14C]-ranitidine were studied in rat and dog after oral administration at a dose level of 50 mg/kg. 5. Urinary excretion was the major elimination pathway for radioactive drug-related material in both species (62-75% of the dose). Unchanged ranitidine was the major radioactive component in both rat and dog urine (0-24 h), accounting for approximately 40% of the dose in each case. 6. In dog, ranitidine undergoes N-oxidation (approximately 30% of dose) whereas in rat, N-oxidation, S-oxidation, N-demethylation and oxidative deamination are all evident, with each metabolite accounting for < 6% of the dose. 7. Two previously unreported metabolites of ranitidine were identified in rat urine using newly developed hplc and lc/ms methods. These metabolites result from single and di-N-demethylation of ranitidine and accounted for 4 and 1% of the dose respectively. | lld:pubmed |
