Age-dependent variations in the distribution of methaqualone in rat

Rats at 1, 4, 8, 12, 20 and 60 postnatal days received orally 5 mg/kg 14C-methaqualone (MTQ) and were sacrificed at 0.5, 1.5 and 6 h. Several tissues were analyzed for unchanged MTQ. In most cases, concentrations reached peak levels at 1.5 h. Highest concentrations were found in the liver followed by the lung, spleen, heart, kidney, eye, and brain. Levels of MTQ were higher in all organs of 1- to 12-day-old rats at all time intervals than the corresponding organs of 20- and 60-day-old rats, apparently resulting from initial higher accumulation and slower rate of disappearance. The 1.5-hour brain:plasma concentration ratio in 8-day-old rats was 0.82 and progressively declined to 0.27 in 60-day-old rats; a similar trend with respect to changes in concentration ratio also occurred for the eye, spleen, kidney, and heart. The fact that the age-related reduction in tissue:plasma concentration ratios occurred in several tissues including brain suggests generalized decreases in tissue accumulation of MTQ. The reduction in brain:plasma concentration ratios, therefore, cannot be ascribed to the blood-brain barrier which develops progressively with the advancing age.