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Comparative plasma concentration profiles after i.v., i.m. and rectal administration of pethidine in children
J Jacobsen1, H Flachs, J O Dich-Nielsen
1Department of Anaesthesia, University of Copenhagen, Rigshospitalet, Denmark.
Insights
Rectal administration of pethidine (an opioid analgesic) in children resulted in significantly lower peak plasma concentrations and reduced overall bioavailability compared to intravenous or intramuscular routes. Rectal pethidine showed approximately 40% systemic availability.
Area of Science:
- Pharmacology
- Pediatric Anesthesiology
- Drug Delivery Systems
Background:
- Pethidine (meperidine) is an opioid analgesic used for pain management.
- Understanding drug pharmacokinetics in pediatric populations is crucial for effective and safe pain relief.
- Different routes of administration can significantly impact drug absorption and systemic availability.
Purpose of the Study:
- To investigate and compare the plasma concentration-time profiles of pethidine and its active metabolite, norpethidine, following intravenous (IV), intramuscular (IM), and rectal administration in children.
- To determine the systemic availability of pethidine when administered rectally in pediatric patients.
Main Methods:
- A study involving 25 pediatric patients post-operation.
- Patients were randomized to receive pethidine 1 mg/kg via IV, IM, or rectal routes.
- Plasma concentrations of pethidine and norpethidine were measured over time to generate concentration-time curves.
Main Results:
- Peak plasma concentrations of pethidine were highest and occurred fastest with IV administration (5 min), followed by IM (10 min), and were significantly lower and delayed with rectal administration (60 min).
- Maximum pethidine concentrations were approximately 2800 nmol/L (IV), 1609 nmol/L (IM), and 531 nmol/L (rectal).
- Area under the curve (AUC) was reduced with rectal administration (P < 0.05), indicating lower overall drug exposure. Rectal administration yielded approximately 40% systemic availability compared to IV, with notable inter-individual variability.
Conclusions:
- Rectal administration of pethidine in children results in slower absorption and significantly reduced systemic availability compared to IV and IM routes.
- The pharmacokinetic profile of rectal pethidine in children is comparable to that observed with other rectally administered opioids.
- While generally lower, significant individual variations in plasma concentrations after rectal administration warrant consideration, potentially due to complex pharmacokinetic factors.
Abstract:
Plasma concentration-time curves of pethidine and norpethidine were studied in 25 children allocated after operation to three groups to receive pethidine 1 mg kg-1 i.v., i.m. or rectally. Peak concentrations occurred after 5 +/- 1, 10 +/- 2, and 60 +/- 10 min, respectively, while the maximum concentrations amounted to 2800 +/- 462, 1609 +/- 367 and 531 +/- 179 nmol litre-1, respectively. The area under the curve (0-240 min) was similarly reduced in the group with rectal administration (P less than 0.05). Compared with the i.v. data, approximately 40% systemic availability occurred after rectal application, although considerable individual variation was noted. In one child very high plasma concentrations were observed after rectal administration, possibly as a result of redistribution/recirculation phenomena. The average results are similar to those obtained when other opioids are given rectally.