Dose-dependent effect of metoclopramide on cholinesterases and suxamethonium metabolism.
In obstetric patients undergoing postpartum tubal ligation, we found that metoclopramide produced dose-dependent prolongation of suxamethonium-induced neuromuscular block. Mean block times after suxamethonium 1 mg kg-1 were 8.0 min, 9.83 min and 12.45 min for control and metoclopramide 10 mg and metoclopramide 20 mg groups, respectively. A laboratory study was therefore conducted on the inhibition of human plasma cholinesterase (PCHE) and erythrocyte acetylcholinesterase (ACHE) activity by varying concentrations of metoclopramide using acetylthiocholine as substrate. PCHE showed a greater sensitivity to inhibition by metoclopramide; the concentration of metoclopramide producing 50% inhibition of activity (I50) was 3.16 x 10(-7) mol litre-1, which is within the therapeutic range. ACHE was less sensitive to inhibition by metoclopramide (I50 2.24 x 10(-5) mol litre-1). Analysis of enzyme kinetics at varying substrate concentrations revealed that metoclopramide produced a potent non-competitive, dose-dependent inhibition of both ACHE and PCHE. The inhibition constant, Ki, was 1.88 x 10(-7) mol litre-1 for PCHE and 9.5 x 10(-8) mol litre-1 for ACHE. As metoclopramide is a potent inhibitor of PCHE, interactions might be expected to occur between metoclopramide and drugs that require PCHE for biotransformation, such as suxamethonium and ester local anaesthetics.
Kao
Y J
YJ
Department of Anesthesiology, Texas Tech University Health Sciences Center, School of Medicine, Lubbock 79430.
Tellez
J
J
Turner
D R
DR
D002800:Cholinesterase Inhibitors / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006801:Humans; D008787:Metoclopramide / Q000494:pharmacology*; D009407:Nerve Block; D049590:Postpartum Period; D011247:Pregnancy; D013390:Succinylcholine / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D013390:Succinylcholine; D008787:Metoclopramide