Some pathways of xenobiotic metabolism in the adult and neonatal marmoset (Callithrix jacchus).

Abstract

1. An oral dose of [carboxyl-14C]benzoic acid was excreted as hippuric acid or benzoylglucuronide by the adult marmoset Callithrix jacchus, and the relative proportions of the metabolites were dose-dependent over the range 1-100mg/kg body weight, the proportion of glucuronideincreasing with increasing dose level. 2. [14C]Aspirin was rapidly absorbed by the marmoset, giving peak blood levels within 1 h of dosing. Unchanged aspirin (trace to 5% dose) was excreted up to 3 h after dosage. Salicylic acid was the major metabolite, relatively little asalicyluric acid was excreted; glucuronic acid conjugates accounted for about 30% of the urinary metabolites and gentisic acid about 2%. 3. p-aminobenzoic acid administered to adult marmosets was excreted as p-acetamidobenzoic acid, the major urinary metabolite, unchanged p-aminobenzoates, p-aminobenzoyl glucuronide and p-aminohippuric acid each representing about 10% of the urinary metabolities; one-fifth of the p-aminohippurate was acetylated. 4. After oral administration of [35S]sulphadiazine to marmosets, peak blood levels of 35S occurred within 5 h dosing, and immediately fell to near-zero values at 24 h. Sulphadiazine and N-acetylsulphadiazine comprised 36% and 34% respectively of the urine 35S while the N1-glucuronide (tentative identification) accounted for 22%. Minor metabolites were the N4-glucuronide and N4-sulphate of sulphadiazine. 5. The extent of acetylation of sulphadimidine by marmosets corresponded to that of fast acetylators in man. 6. The metabolism of [14C]benzoate and of p-aminobenzoic acid in the neonatal marmoset was compared with that in similarly dosed neonatal rats.