Clinical pharmacology and therapeutics
-
Clin. Pharmacol. Ther. · Jun 2006
Clinical TrialPharmacokinetics of midazolam, propofol, and fentanyl transfer to human breast milk.
Lactating women undergoing operations requiring general anesthesia are advised to pump and discard their milk for 24 hours after the procedure. Data on anesthetic drug transfer into breast milk are limited. This study determined the pharmacokinetics of midazolam, propofol, and fentanyl transfer into milk to provide caregivers with data regarding the safety of breast milk after administration of these drugs. ⋯ The amount of midazolam, propofol, and fentanyl excreted into milk within 24 hours of induction of anesthesia provides insufficient justification for interrupting breast-feeding.
-
Clin. Pharmacol. Ther. · Apr 2006
Randomized Controlled TrialAnalgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism.
Preclinical studies have suggested that the mechanism of the analgesic action of acetaminophen (INN, paracetamol) is linked to the serotonergic system and that it is inhibited by tropisetron, a 5-hydroxytryptamine type 3 antagonist. The aim of this study was to confirm these findings in humans. ⋯ These results clearly show for the first time in humans that the coadministration of tropisetron or granisetron with acetaminophen completely blocks the analgesic effect of acetaminophen. They support the hypothesis that the mechanism of the analgesic action of acetaminophen might involve the serotonergic system. Furthermore, they demonstrate a pharmacodynamic interaction between these 2 types of drugs, which are frequently coadministered, especially in cancer patients.
-
Clin. Pharmacol. Ther. · Apr 2006
Clinical TrialEnvironmental and genetic factors associated with morphine response in the postoperative period.
The aim of this study was to investigate the respective influence of genetic and nongenetic factors on morphine dose requirements and adverse effects after colorectal surgery. ⋯ Age and prior use of psychotropic agents are associated with postoperative morphine dose requirements. Whether ABCB1 polymorphisms might predict morphine side effects remains to be determined.
-
Clin. Pharmacol. Ther. · Mar 2006
Randomized Controlled TrialThe angiotensin II receptor antagonist valsartan inhibits endothelin 1-induced vasoconstriction in the skin microcirculation in humans in vivo: influence of the G-protein beta3 subunit (GNB3) C825T polymorphism.
We investigated the influence of angiotensin II receptor blockade on angiotensin II-induced, endothelin 1 (ET-1)-induced, and norepinephrine-induced vasoconstriction to further characterize interactions of the 3 major pressor systems. ET-1, angiotensin II, and norepinephrine act via G protein-coupled receptors with a possible involvement of the G-protein beta3 subunit (GNB3) C825T polymorphism. We studied the influence of this polymorphism on the responses to angiotensin II antagonism in the presence of ET-1, norepinephrine, and angiotensin II. ⋯ Our results indicate that the renin-angiotensin system may significantly contribute to ET-1-mediated microvascular responses. Valsartan inhibited local vasoconstriction to angiotensin II and ET-1 to a greater degree in carriers of the GNB3 825T allele, which adds to data from earlier studies implicating the C825T polymorphism as a pharmacogenetic marker for drug effects.