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 1–100 mg/kg body weight, the proportion of glucuronide increasing 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 salicyluric 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 of 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.