title: Intravenous morphine pharmacokinetics in pediatric patients with sickle cell disease.
abstract: 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.
authors.affiliation: Marian Anderson Sickle Cell Anemia Care and Research Center, St. Christopher's Hospital for Children, Philadelphia, PA 19134-1095.
authors.forename: C D
authors.initials: CD
authors.lastname: Dampier
authors.forename: B N
authors.initials: BN
authors.lastname: Setty
authors.forename: J
authors.initials: J
authors.lastname: Logan
authors.forename: J G
authors.initials: JG
authors.lastname: Ioli
authors.forename: R
authors.initials: R
authors.lastname: Dean
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology
chemical_list: D009020:Morphine