Abstract

The distribution of N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR) and its metabolites was investigated in the liver, serum, mammary gland, and urinary bladder of female rats and mice. Following an iv dose of 5 mg/kg to rats, 4-HPR distributed to all tissues examined with the highest levels reached in the liver. The distribution period was completed in about 4 hr and was followed by first order elimination kinetics. The t1/2 for 4-HPR elimination from the liver was 9.4 hr, from the serum was 12.0 hr (not significantly different from liver), from the mammary gland was 43.6 hr, and from the urinary bladder was 9.3 hr. A 5-day ip dosing study (5 mg/kg/day of 4-HPR) in both rats and mice revealed that 4-HPR distributed to all tissues examined with the highest levels reached in the urinary bladder. 4-HPR and four metabolites were detected in the tissues. One coeluted with a cis isomer of 4-HPR (M2), another with N-(4-methoxyphenyl)-all-trans-retinamide (4-MPR) (M3), a third appeared to be a 4-HPR-ester (M4), and the fourth remains unidentified (M1). However, the amount of each metabolite varied between tissues and between species. The concentration of 4-HPR was significantly 2-4 times lower and the percentage of M3 (4-MPR) was 3 times higher in the mouse tissues than in the corresponding tissues of the rat. M2 (cis-4-HPR) and M4 (4-HPR-ester) were present in rat liver but not in mouse liver.(ABSTRACT TRUNCATED AT 250 WORDS)