The metabolic fate of tizoprolique acid in baboons

Abstract

1. After oral administration of the anti-lipolytic drug [¹⁴C]tizoprolique acid (2-propyl-5-carboxy1[4-¹⁴C]thiazole), to baboons (60 mg/kg), the radioactivity was well absorbed and rapidly excreted. During 6 and 24 h respectively, 60±25% (S.D.) and 90±2% were excreted in the urine.

2. Plasmaconcn. of ¹⁴C reached a max. (182±65, range 85–221 ±g equiv./ml) at 1–1.5 h after an oral dose, and declined rapidly with an apparent half-life of about 0.5 h. A mean of 77±7% of the ¹⁴C in peak plasma samples was bound to plasma proteins, somewhat less than that of [¹⁴C]tizoprolique acid (84±5%).

3. Tissue concn. of ¹⁴C were highest in an animal killed at 0.5 h after an oral dose, but were lower than those in plasma in all tissues examined except the kidneys.

4. The major metabolite of tizoprolique acid was its glycine conjugate, which accounted for about 80% dose excreted in the 24h urine. About 2% dose was excreted as unchanged drug. About 70% and 20% respectively of plasma ¹⁴C were associated with the unchanged drug and its glycine conjugate during the period 15 min to 4h after dosing.