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Pharmacokinetics, blood partition, and tissue distribution of itraconazole.

Pharmacokinetics of itraconazole was measured after 1-min intravenous infusion at a dose of 10 mg/kg to male New Zealand white rabbits. The terminal half-life of itraconazole was 524 min. Itraconazole was eliminated slowly in rabbits with total body clearance of 3.26 ml/min/kg. Blood partition of itraconazole between plasma and blood cells of rabbit blood was measured. Itraconazole reached equilibrium rapidly between plasma and blood cells of rabbit blood. The equilibrium plasma/blood cells concentration ratios were independent of initial rabbit blood concentrations of itraconazole, 1, 5, and 10 microg/ml; the mean value was 3.25. Tissue distribution of itraconazole was also measured after 1-min intravenous administration at a dose of 10 mg/kg to rats. The tissue-to-plasma (T/P) ratios of itraconazole were greater-than-unity in all rat tissues studied at both 1 and 24 h except in fat and stomach at 1 h. This indicated that rat tissues studied had a high affinity to itraconazole.