Pharmacokinetics of morphine in plasma and discrete areas of the rat brain

After intravenous administration of an analgesic dose of morphine into rat, the time course of morphine concentrations was followed in plasma, whole brain, and four discrete areas of the brain during 8 hr. These concentration curves indicated a three-exponential function which could be described by a mammillary system of three compartments. Maximal brain levels were obtained 15–20 min after injection, showing a fairly even distribution pattern of morphine. The plasma to whole brain ratio showed three-exponential characteristics, approaching a constant value of about 4.7–4.8 after 4 hr. By use of the SAAM-25 program, the experimental data from plasma and brain were simultaneously fitted to five separate sets of three-compartment models. Results obtained implied the uniqueness of the computed transfer constants of the three-compartment model.