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Technology Information:

Pharmacokinetics of M6G following intravenous and oral administration [An article from: Acute Pain

Description

This digital document is a journal article from Acute Pain, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser.

Abstract:
Background: The active metabolite of morphine, morphine-6-glucuronide (M6G), shows an analgesic effect that is equivalent to morphine. The bioavailability is low (11-13%) when given orally due to poor absorption from the GI-tract and further the absorption seems to be biphasic. The aims of this study were to determine the pharmacokinetics after intravenous administration (i.v.) of M6G in humans, to elucidate the absorption profile of M6G after oral administration, and to evaluate if the bioavailability could be increased by co-administration of the absorption enhancer Tween 20. Methods: The study was a non-blinded randomised balanced three-way crossover study in eight healthy male subjects. The subjects received 25mg i.v. M6G, 200mg oral M6G, and 50mg oral M6G+500mg of Tween 20. Blood samples were collected until 12h after i.v. administration and until 24h after oral administration. Paracetamol and sulfasalzine were co-administered with oral administrated M6G as markers for when the gut contents reached the duodenum and colon, respectively. Results: The pharmacokinetic profile of i.v. M6G was in close agreement with previously reported data (t"1"/"2 0.93+/-0.2h, CL 157+/-8ml/min, V"d","s"s 13.2+/-3.5l, and AUC"0"-"~ 5341+/-289nmol/l/h). After oral administration, neither bioavailability nor time to the first or second peak changed in the presence or absence of Tween 20 (F: 9.3+/-2.4 and 10.1+/-4.8%; t"1: 2.5 [1.0-6.1] and 5.0 [2.0-8.2]h; and t"2: 18.0 [11.0-20.0] and 20.0 [11.0-24.0]h, respectively). Conclusion: In this study, the pharmacokinetic profile of M6G was found to be in agreement with profiles found by others. Two different plasma concentration peaks were found after oral administration of M6G, the second of which occurred after the gut contents reached colon. Co-administration of Tween 20 did not enhance the bioavailability.

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