Metabolism of phenformin in the rat and guinea-pig.

1. Following administration of [2'-14C]phenformin to rat and guinea pig, the guinea-pig showed a slower rate of excretion of radioactivity than the rat, together with a slower rate of metabolism, which may partly explain the increased pharmacological response of the guinea-pig to the drug. 2. The rat eliminated 26% of an intraduodenal dose of [2'-14C]phenformin (20 mg/kg) in the bile in 6 h compared to 6% in the guinea-pig. 3. The rat excreted large amounts of 4-hydroxyphenformin (free and conjugated with glucuronic acid) and also some unchanged phenformin, but the extent of metabolism varied with dose and route of administration. 4. The guinea-pig excreted no 4-hydroxyphenformin after an oral dose (25 mg/kg) and only a small amount after i.p. administration (12.5 mg/kg). After oral administration, guinea-pig urine contained an unidentified metabolite, and its glucuronide, which may be a product of aliphatic C- or N-hydroxylation and which accounted for 47% of the 24 h urinary radioactivity (17% of the dose). Guinea-pig faeces contained an unidentified metabolite which had similar chromatographic properties to the novel urinary metabolite.