Intravenous morphine pharmacokinetics in pediatric patients with sickle cell disease

To examine the pharmacokinetics of parenteral opioids, such as morphine, in patients with sickle cell disease, we determined the plasma morphine clearances in 18 patients (aged 6 to 19 years) who were receiving continuous intravenous infusions, and the pharmacokinetics of morphine in an additional six patients after single intravenous doses. Plasma morphine clearances ranged from 6.2 to 59.1 ml min-1 kg-1 (35.5 +/- 12.4, mean +/- SD) during steady-state infusions. There was a negative correlation between clearance values and age over the age range studied (p = 0.013). A significant difference (p = 0.042) was also observed in clearance values between patients who had serious adverse symptoms (23.4 +/- 10.7 ml min-1 kg-1) and those who had less serious symptoms (36.3 +/- 6.4 ml min-1 kg-1) when morphine was given at high dosage rates (> or = 0.15 mg kg-1 hr-1). Pharmacokinetic modeling of plasma morphine concentrations adequately fit a two-compartment model with a short initial distribution phase (mean half-life = 4.5 minutes) and a rapid terminal elimination half-life (77.6 +/- 19.2 minutes). These findings suggest that considerable individualization of morphine dosing may be necessary to achieve optimal analgesia and minimal adverse effects in these patients.