Pharmacokinetics of the trichothecene mycotoxin verrucarol in dogs

Verrucarol is a simple trichothecene which is structurally related to T-2 and HT-2 toxins. Several macrocyclic trichothecenes which are ester derivatives of verrucarol possess antitumor activity. The pharmacokinetics of verrucarol has been studied in eight dogs following iv and oral administrations (0.4 and 0.8 mg/kg, respectively). The iv study showed that verrucarol has a mean (+/- SD) clearance of 11 +/- 5.5 mL/min/kg, a volume of distribution of 1.2 +/- 0.6 L/kg, and a terminal half-life of 1.6 +/- 0.5 h. Following oral administration, the absolute bioavailability of verrucarol was 44 +/- 33%, and its terminal half-life was similar to that obtained after iv administration. In comparison with T-2 and HT-2 toxins, verrucarol has a longer half-life and a lower clearance, and its liver extraction ratio is about one third of that of T-2 and HT-2 toxins. Therefore, verrucarol is less susceptible to a liver first-pass effect and its partially absorbed after oral administration. These characteristics make verrucarol the first partially absorbed trichothecene whose pharmacokinetics was investigated following oral administration.