Lack of interaction between metoclopramide and morphine in vitro and 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 (µM), 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.

Keywords: :

• Morphine
• metoclopramide
• gastroparesis
• drug–drug interaction
• glucuronidation