Lack of interaction between metoclopramide and morphinein vitroand in mice

Abstract

1. This study examined interactions via common metabolism or via common pharmacodynamic pathways between frequently co-prescribed metoclopramide (a prokinetic) and morphine (an opioid analgesic). 2. In human liver microsomes, morphine 3-glucuronide and morphine 6-glucuronide formation had V(max) estimates of 6.2 +/- 0.07 and 0.75 +/- 0.01 (nmole min(-1) mg(-1) protein) and K(m) estimates of 1080 +/- 37 and 665 +/- 55 (microM), respectively. The in vitro K(i) for morphine 3-glucuronide formation in the presence of metoclopramide in human liver microsomes or recombinant uridine diphosphoglucuronosyltransferase 2B7 predicted a lack of in vivo interaction. 3. Morphine (2 mg kg(-1) subcutaneously) delayed gastrointestinal meal transit in mice, metoclopramide (10 mg kg(-1) subcutaneously) had no effect on meal transit, and metoclopramide did not alter this effect of morphine. 4. Morphine (2 or 5 mg kg(-1) subcutaneously) was antinociceptive in mice (hot plate test) and metoclopramide (10 mg kg(-1) subcutaneously) did not alter the antinociceptive effects of morphine. 5. Together, the data suggest a lack of interaction between morphine and metoclopramide.

Analgesic Effects of Morphine in Combination with Adjuvant Drugs in Rats

“…Metoclopramide is suggested to potentiate morphine analgesia [19] through the interaction with opioid receptors [20] and other putative mechanisms [21]; nonetheless more recent experimental studies [22] and clinical data [23] do not support these hypotheses, which is in line with our results. However, it should be noted that conflicting results on morphine and metoclopramide analgesic interaction might be due to different dosing schedules and rat strains used in the aforementioned experimental studies.…”

<i>In Vivo</i> Interaction of Morphine and Diclofenac

“…Pharmacokinetic parameters calculated from plasma concentrations of morphine after subcutaneous administration (5 mg/kg) in rats pretreated with vehicle or diclofenac (5 mg/kg, intraperitoneal). pharmacokinetic interaction (AUCi/AUC >2) [12]. After a single dose administration of morphine and diclofenac in rats, the serum concentrations of morphine and, moreover, its glucuronide (M3G) were increased.…”