Abstract
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.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|