The single-dose pharmacokinetics and bioavailability of three ketoconazole formulations were evaluated using HPLC in five healthy human volunteers and six male mongrel dogs. The human volunteers received 400 mg PO of ketoconazole as tablet (Ktab) and solution (K-,) formulations. The dogs received 400 mg PO of Ktab and L,, and 376 mg iv of an intravenous dose (KJ. In humans the AUC value for K , , (62.21 2 21.2 pg . h/mL; mean * SD) was significantly greater than for Ktab (50.0 ? 15.2 pg . h/mL; p <0.05). Peak serum concentrations (Cmax), time to peak serum concentrations (tmax), ti,2, and the terminal elimination rate constant (k,) did not differ between Klab and K-,. This suggests that the administration of Kso, may be a useful alternative to dosage increases in situations where low bioavailability of ketoconazole in tablet form is suspected. The mean systemic clearance (CL) of K,, in dogs was 2.74 f 1.10 mL/min/kg, the volume of distribution at steady state (Vd,,) was 0.72 2 0.28 Ukg, and the half-life was 2.7 2 1.6 h. Considerable variability was seen in the AUC of ketoconazole, particularly with the oral preparations. The absolute bioavailability of K, , , was 0.50 ? 0.38, which did not differ statistically from that of K, , , 0.56 2 0.23. The K, , , showed less variability in AUC, C , , , and F values than did Ktab, and two dogs with low bioavailability with K , , ,
04 and 0.07) had substantially greater bioavailability with Kwl (F = 0.96 and 0.57, respectively). Evaluation of K, , in dogs confirms decreased bioavailability from orally administered tablet formulations of ketoconazole.