Rectal administration of morphine in children. Pharmacokinetic evaluation after a single-dose.
BACKGROUND
There is limited knowledge about the pharmacokinetics of morphine and its metabolites after rectal administration in children. In this study the pharmacokinetics of two different rectal formulations of morphine were examined and compared with intravenous morphine.


METHODS
Children undergoing elective surgery received rectal morphine 0.2 mg/kg before start of surgery. Ten children (mean age 14 months) received morphine rectally in a hydrogel formulation and another 10 children (mean age 16 months) received morphine rectally in a parenteral formulation. For comparison, 6 children (mean age 21 months) were given the same dose intravenously. The plasma concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured by HPLC over 6 h after drug administration.


RESULTS
The mean rectal bioavailability of morphine was 35% (range 18-59) after hydrogel administration and 27% (range 6-93) after the solution. Mean values of Cmax were 76 nmol/l (25-129) and 56 nmol/1 (15-140), respectively. The results showed that morphine gel had a significantly higher bioavailability (P < 0.02) than the solution. The ratios of plasma (M3G + M6G) to morphine were higher after rectal administration (mean 7.5-8.7) than after i.v. injection (mean 5.3), indicating the presence of first-pass metabolism using the rectal route.


CONCLUSIONS
The rectal morphine hydrogel has pharmacokinetic properties which makes it a useful formulation for premedication and pain alleviation in paediatric patients.
Lundeberg
S
S
Department of Paediatric Anaesthesia, St Görans Children's Hospital, Stockholm, Sweden.
Beck
O
O
Olsson
G L
GL
Boreus
L O
LO
D000285:Administration, Rectal; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000493:pharmacokinetics
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide