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Hasegawa, Y., Kishimoto, S., Shibatani, N., Nomura, H., Ishii, Y., Onishi, M., Inotsume, N., Takeuchi, Y. and Fukushima, S. (2010) The Pharmacokinetics of Morphine and Its Glucuronide Conjugate in a Rat Model of Streptozotocin-Induceddiabetes and the Expression of MRP2, MRP3 and UGT2B1 in the Liver. Journal of Pharmacy and Pharmacology, 62, 310-314.
https://doi.org/10.1211/jpp.62.03.0004

has been cited by the following article:

• TITLE: In Vivo Interaction of Morphine and Diclofenac

  AUTHORS: Yoshiaki Kimura, Koki Muryoi, Mika Shibata, Noriyuki Ozaki, Kunizo Arai

  KEYWORDS: Morphine, Diclofenac, Udp-Glucuronosyltransferase, Von Frey Test

  JOURNAL NAME: Pharmacology & Pharmacy, Vol.7 No.12, December 30, 2016

  ABSTRACT: The number of studies on possible pharmacokinetic interactions between opioid analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used in combination for the treatment of chronic pain, is limited. In rats, the major metabolic pathway of morphine is glucuronidation to morphine-3-glucuronide (M3G) by UDP-glucuronosyltransferase. In this study, we investigated the influence of diclofenac (NSAID) on the formation of M3G in vitro using rat liver tissue homogenates. Competitive inhibition of M3G formation by diclofenac was observed with an average Ki of 19.9 μM. Because these in vitro findings suggested that a pharmacokinetic interaction occurs in vitro , we investigated whether diclofenac inhibits the glucuronidation of morphine in rats. A single dose of diclofenac increased serum concentrations of both morphine and M3G and showed a higher analgesic efficacy in the Von Frey test. Furthermore, diclofenac caused a net decrease in morphine urine concentrations, but the excretion of M3G through biliary and urinary routes was unchanged. These results demonstrated that in contrast to in vitro data a single dose of diclofenac did not alter the glucuronidation of morphine in vitro .