RECTAL ADMINISTRATION OF MORPHINE IN CHILDREN - PHARMACOKINETIC EVALUATION AFTER A SINGLE-DOSE

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: Childr en undergoing elective surgery received rectal morphine 0.2 mg/kg befo re start of surgery. Ten children (mean age 14 months) received morphi ne rectally in a hydro-gel formulation and another 10 children (mean a ge 16 months) received morphine rectally in a parenteral formulation. For comparison, 6 children (mean age 21 months) were given the same do se intravenously. The plasma concentrations of morphine, morphine-3-gl ucuronide (M3G) and morphine-g-glucuronide (M6G) were measured by HPLC over 6 h after drug administration. Results: The mean rectal bioavail ability of morphine was 35% (range 18-59) after hydrogel administratio n and 27% (range 6-93) after the solution. Mean values of Cmax were 76 nmol/l (25-129) and 56 nmol/l (15-140), respectively. The results sho wed that morphine gel had a significantly higher bioavailability (P<0. 02) than the solution. The ratios of plasma (M3G + M6G) to morphine we re higher after rectal administration (mean 7.5-8.7) than after i.v. i njection (mean 5.3), indicating the presence of first-pass metabolism using the rectal route.Conclusions: The rectal morphine hydrogel has p harmacokinetic properties which makes it a useful formulation for prem edication and pain alleviation in paediatric patients.