Could pharmacogenetic data explain part of the interindividual sensitivity to methadone-induced respiratory depression?
In this issue of Critical Care, Megarbane and colleagues present a case report of methadone-induced respiratory depression and conduct a toxicokinetic/toxicodynamic evaluation. An opioid-dependent patient receiving methadone maintenance treatment (daily dose 70 mg) was found unconscious after ingesting 240 mg methadone and 2 mg flunitrazepam. Significant improvement in consciousness was achieved after an intravenous bolus of 0.3 mg naloxone followed by a continuous infusion of naloxone at 0.3 mg/hour. In patients receiving methadone maintenance treatment, an occasional intake of two to four times the usual daily dose of methadone is not an exceptional occurrence. However, few such patients experience episodes of life-threatening respiratory depression. Here, we discuss whether recent pharmacogenetic data could help us to understand interindividual variability in sensitivity to respiratory depression and, ultimately, to predict which patients are most likely to be affected.
Crettol
Séverine
S
Unit of Biochemistry and Clinical Psychopharmacology, Centre for Psychiatric Neurosciences, University Psychiatry Department, Cery Hospital, CH-1008 Prilly-Lausanne, Switzerland.
Monnat
Martine
M
Eap
Chin B
CB
D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D008691:Methadone / Q000009:adverse effects*; D009294:Narcotics / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D017450:Receptors, Opioid, mu / Q000235:genetics; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000235:genetics; D012307:Risk Factors
D009294:Narcotics; D017450:Receptors, Opioid, mu; D003577:Cytochrome P-450 Enzyme System; D008691:Methadone