Absorption of diazepam and its transfer through the blood-brain barrier after intraperitoneal administration in the...

Unlabeled diazepam of 0.9 mg/kg was administered i.p. to the rat of 21 days of age with a trace amount of [N-methyl-3H] diazepam and the drug concentrations in the blood and the brain tissues were determined at various time intervals. A two-compartment open model was applied and the absorption and distribution rate constants were distinctly determined on the theoretical basis established in the present study with the aid of a computer. The specific rate constants for absorption, distribution (k12 and k21) and elimination were 0.158, 0.015 and 0.136 and 0.013/min, respectively. A full description of the drug concentration in the central compartment as a function of time enabled us to calculate directly the transfer rate constants between the blood and the brain (k'12 and k'21), resulting in 4.49 and 2.66/min on the average of the five regions in the brain. A time-dependent change of the rate constants through the blood-brain barrier was suggested from a computer simulation.