Figure 4.

Co-administration of ketoconazole increased systemic N-(4-hydroxyphenyl)retinamide (4-HPR) levels in mice in vivo. (A) 4-HPR and N-(4-methoxyphenyl)retinamide (4-MPR) levels in plasma of nu/nu mice given 4-HPR with increasing doses of ketoconazole. The mice were killed 4 h after the ninth dose. (B) 4-HPR and 4-MPR levels in plasma of non-obese diabetic/severe combined immune deficiency (NOD/SCID) mice given 4-HPR with increasing doses of ketoconazole. Assay times were the same as described for Figure 4A. (C) 4-HPR, 4-MPR and 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) levels in plasma of NOD/SCID mice given 4-HPR alone or with ketoconazole (25 mg·kg⁻¹). Mice in both groups were killed 4 h after the fifth dose. In panels A–C, all mice received 4-HPR (180 mg·kg⁻¹ per day) gavaged in two divided doses; control mice for all experiments received 4-HPR without ketoconazole. Cohorts of three mice were used for each condition and columns are the mean and error/vertical bars are standard deviation from experiments performed in triplicate. *P < 0.02, **P < 0.01.