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 (greater than or equal to 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.