Effect of itraconazole on the pharmacokinetics of all-trans-retinoic acid in rabbits

OBJECTIVE: To investigate the effect of itraconazole on the pharmacokinetics of all-trans-retinoic acid (ATRA). METHODS: ATRA (10 mg) alone and simutaneously with itraconazole (10 mg + 30 mg) were administered orally in a randomized, cross-over way. A reversed-phase high performance liquid chromatographic method was established for the determination of ATRA in serum. RESULTS: The pharmacokinetics of ATRA conformed to a one-compartment open model. The main pharmacokinetic parameters after the oral administration alone and combination were as follows: cmax were (113.83 ± 62.65) ng&middotmL-1 and (281.91 ± 75.40) ng&middotmL-1 (Pmax were (3.67 ± 0.50) h and (2.11 ± 0.60) h (P0∼∞ were (374.9 ± 179.5) ng&middoth&middotmL-1 and (675.5 ± 212.6) ng&middoth&middotmL-1 (0.011/2ke were (2.40 ± 0.98) h and (1.91 ± 1.26) h (P>0.05), respectively. CONCLUSION: There was significant effect of itraconazole on the pharmacokinetics of ATRA, the cmax and AUC of ATRA were increased by the combination. The use of ATRA in combination with itraconazole merits further investigation.