METABOLISM, PLASMA OR SERUM LEVELS, AND ELIMINATION OF PHENFORMIN IN GUINEA-PIGS, RATS, AND DOGS

14C‐Phenformin hydrochloride was used for investigating the metabolism, plasma or serum levels, and elimination of the drug following 1.5‐mg/kg po or iv doses to guinea pigs, rats, and dogs. The amounts of individual metabolites and unchanged drug were assessed in urine as well as in plasma or serum. The glucuronide of 1‐(p‐hydroxyphenethyl)biguanide was a major metabolite in the blood and urine of all three species. Guinea pig serum and urine contained a sizable quantity of unchanged drug. Dog plasma and urine had significant amounts of nonconjugated 1‐(p‐hydroxyphenethyl)biguanide and of an unidentified major metabolite. In all three species following intravenous drug administration, unchanged drug contributed significantly to the radioactivity found in blood and urine. The apparent half‐lives of phenformin elimination were 0.3‐0.8 day for guinea pigs and rats and 1‐1.5 days for dogs. Urinary excretion data indicate apparent half‐lives of approximately 1.3‐1.5 days for the elimination of each of the three major metabolites in dogs. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company