Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain

Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain

Hunt A; Joel S; Dick G; Goldman A

Journal Of Pediatrics

1999

Child; Analgesics; Age Factors; Linear Models; Case-Control Studies; adolescent; Preschool; Non-U.S. Gov't; infant; Comparative Study; Nonparametric; Statistics; Dose-Response Relationship; Drug; Delayed-Action Preparations; Human; Support; Neoplasms/complications; Morphine Derivatives/administration & dosage/blood/pharmacokinetics; Morphine/administration & dosage/blood/pharmacokinetics; Opioid/administration & dosage/blood/pharmacokinetics; Pain/drug therapy/etiology

OBJECTIVES: (1) To determine the pharmacokinetics of morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) in children with cancer receiving morphine as immediate-release morphine liquid or sustained-release tablets. (2) To determine differences with age within the group and from adults. (3) To explore relationships between plasma concentration and pain measurements. STUDY DESIGN: Blood samples were collected and plasma analyzed by high-performance liquid chromatography with electrochemical and fluorescence detection. Population pharmacokinetic parameters were derived with the program P-PHARM. RESULTS: Forty children with a median age of 11.4 years (range 1.7 to 18.7 years) received a median dose of 1.4 mg/kg/d (range 0.4 to 24.6 mg/kg/d). A median of 4 blood samples per child was collected. Plasma clearance of morphine was 23.1 mL/min per kg body weight. The volume of distribution was 5.2 L/kg. Molar ratios of M3G/morphine, M6G/morphine, and M3G/M6G were 21.1, 4.7, and 4.2, respectively. Children 12 ng/mL in children with cancer pain unrelieved by mild to moderate strength analgesia.

1999

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