INTRAVENOUS MORPHINE PHARMACOKINETICS IN PEDIATRIC-PATIENTS WITH SICKLE-CELL

To examine the pharmacokinetics of parenteral opioids, such as morphin e, in patients with sickle cell disease, we determined the plasma morp hine clearances in 18 patients (aged 6 to 19 years) who were receiving continuous intravenous infusions, and the pharmacokinetics of morphin e 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 negat ive correlation between clearance values and age over the age range st udied (p = 0.013), A significant difference (p = 0.042) was also obser ved in clearance values between patients who had serious adverse sympt oms (23.4 +/- 10.7 ml min(-1) kg(-1)) and those who had less serious s ymptoms (36.3 +/- 6.4 ml min(-1) kg(-1)) when morphine was given at hi gh dosage rates (greater than or equal to 0.15 mg kg(-1) hr(-1)). Phar macokinetic 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 (7 7.6 +/- 19.2 minutes). These findings suggest that considerable indivi dualization of morphine dosing may be necessary to achieve optimal ana lgesia and minimal adverse effects in these patients.