European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Aug 2009
Randomized Controlled TrialO-demethylation of codeine to morphine inhibited by low-dose levomepromazine.
Codeine/paracetamol (C/P) and levomepromazine (L) are frequently co-administered for the treatment of acute back pain, but the efficacy/effectiveness of this combination drug therapy has not been evaluated. The demethylation of codeine to morphine is catalyzed by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6), of which levomepromazine (methotrimeprazine) is a known inhibitor. The aim of this study was to investigate whether low-dose levomepromazine inhibits the formation of morphine from codeine in a patient population of homozygous extensive (EM) and heterozygous extensive (HEM) metabolizers of CYP2D6. ⋯ Our study revealed significant inhibition in the O-demethylation of codeine to morphine in homozygous EM of CYP2D6 treated with low-dose levomepromazine and codeine/paracetamol, compared to treatment with codeine/paracetamol only. No significant difference could be detected in HEM or in the mixed and heterogenous group of EM/HEM. In patients prescribed this drug combination, the amount of morphine generated by the O-demethylation of codeine may be insufficient for effective pain relief. The therapeutic effect of codeine in the treatment of acute back pain should be assessed with and without levomepromazine.
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Eur. J. Clin. Pharmacol. · Aug 2009
Distribution of fentanyl in the placental intervillous space and in the different maternal and fetal compartments in term pregnant women.
Fentanyl is used in obstetrical practice to promote analgesia and anesthesia during labor and in cesarean delivery, with rapid and short-term effects. ⋯ The present study demonstrated that the placental intervillous space acted as a site of fentanyl deposit, a fact that may be explained by two hypotheses: (1) the blood collected from the placental intervillous space is arterial and, according to some investigators, the arterial plasma concentrations of the drugs administered to patients undergoing epidural anesthesia are higher than the venous concentrations, and (2) a possible role of P-glycoprotein (P-gp).