Pharmacokinetics of Morphine

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Abstract
The disposition of morphine in serum and that in the cerebral cortex during normocarbia and hypercarbia were determined in dogs. Normocarbia (pHa (arterial pH) 7.41; PaCO2, partial arterial pressure CO2, 36 torr) was maintained by controlled ventilation. Hypercarbia (pHa, 7.15; PaCO2, 69 torr) was induced by inhalation of 10% CO2, balance O2. After achievement of a steady acid-base status, morphine sulfate, 2 mg/kg, was injected i.v. Thereafter, serial samples of serum and cerebral cortex were taken at intervals for as long as 4 h and analyzed for morphine concentration using radioimmunoassay. Serum morphine concentrations 2 and 5 min following i.v. injection were higher in dogs with hypercarbia, although the serum half-life during the elimination phase remained unchanged, 65-67 min. The initial volume of distribution, Vi, was smaller during hypercarbia. During hypercarbia morphine concentrations in the cerebral cortex were significantly higher at 15, 60, 120 and 240 min than those found during normocarbia. The half-lives of morphine in the cerebral cortex were 4.1 h during normocarbia and 6.9 h during hypercarbia. The initial higher drug concentrations in the serum and the increased cerebral blood flow during hypercarbia may facilitate the penetrance of morphine into the brain. Once in the brain, a greater proportion of morphine was probably present in the protonated form and thus less able to pass through lipid barriers back into the circulation.

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