Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites

The disposition of parenteral morphine was assessed in two pharmacokinetic studies. In Study 1, 10 mg of morphine sulfate was administered by intravenous (IV) infusion, intramuscular (IM) injection, or both, to 8 healthy young adult male volunteers. Plasma morphine concentrations were determined by radioimmunoassay in multiple blood samples drawn after each dose. Mean (+/-SE) kinetic parameters following IV morphine were: volume of distribution (Vd), 3.2 (+/- 0.3) L/kg; elimination half-life (t1/2beta), 2.9 (+/- 0.5) hr; clearance, 14.7 (+/- 0.9) ml/min/kg; extraction ratio, 0.70 (+/- 0.04). After IM morphine, peak plasma levels ranged from 51 to 62 ng/ml and were reached within 20 min of injection. The absorption half-life averaged 7.7 (+/- 1.6) min. Systemic availability was 100% complete. In study 2, 4 elderly male patients (61 to 80 yr of age) received 45 to 80 mg of morphine sulfate IV prior to operative repair of an abdominal aortic aneurysm. Morphine pharmacokinetics were determined as described above. Kinetic variables were Vd, 4.7 (+/- 0.2) L/kg; t1/2beta, 4.5 (+/- 0.3) hr; clearance, 12.4 (+/- 1.2) ml/min/kg; extraction ratio, 0.59 (+/- 0.05). Both studies demonstrate that morphine distribution is rapid and extensive and its t1/2beta relatively short. IM morphine is rapidly and completely absorbed.