Therapeutic drug monitoring
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The pharmacokinetics of propofol was studied in 11 Asian patients with fentanyl-isoflurane anaesthesia during cardiopulmonary bypass (CPB) and undergoing elective coronary artery bypass grafting (CABG). Instead of the usual increments of morphine and a benzodiazepine, propofol (4 mg/kg/h) was initiated at the start of CPB and ceased at CPB separation. Whole blood propofol concentrations were determined during and postinfusion using high-performance liquid chromatography with fluorescence detection. ⋯ The mean clearance of 1.31 (0.50) L/min was lower than those reported from other studies, whereas the mean blood concentration of 2.2 (1.0) mg/L at the 1-h infusion period was higher. The mean calculated apparent Css was 3.9 (1.5) mg/L. The low clearance is likely to be due to hemodynamic changes during CPB and CABG, thereby affecting drug distribution and blood flow to the liver.
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Consumption of ethanol during the course of cocaine binges is common, with an estimated prevalence well in excess of 50%. Cocaine abusers indicate that coingestion of ethanol may enhance and/or prolong the euphoria and reduce unpleasant side effects that may follow. ⋯ However, cocaine and cocaethylene also appear to differ in some respects, including the relative potency of their actions on the dopamine and serotonin transporters. Information obtained from animal and human studies of the neurochemical and behavioral properties of cocaethylene and of cocaine-ethanol interactions is reviewed, and the possible implications with respect to the mechanisms and consequences of combined cocaine and ethanol abuse are described.
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There is an increased use of extracorporeal membrane oxygenation (ECMO) in the last 15 years for critically ill neonates. While receiving ECMO therapy, the critically ill infant needs various medications. We performed an in vitro study to evaluate the potential effect of the membrane oxygenator on drug extraction. ⋯ In a child receiving 20 micrograms/kg/h infusion of morphine, steady-state concentrations of 68.2 ng/ml fell to 11.6 ng/ml after changing the membrane. Our data indicate that the ECMO is associated with lowering of the concentrations of commonly used medications and that this process may depend partially on how new the membrane is. Before these changes may lead to new dosing guidelines for small children receiving ECMO, more experiments with new and used systems are warranted, as well as with different types of ECMO.
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The effectiveness of caffeine citrate in preventing idiopathic apnea in premature infants was evaluated. Thirty-seven preterm infants born before the 32nd week of gestation were studied. After an intravenous loading dose of 10 mg/kg of caffeine citrate, two different oral maintenance regimens were followed: 5 mg/kg in Group I and 2.5 mg/kg in Group II. ⋯ In Group II, the frequency of side effects such as tachycardia and gastrointestinal intolerance was significantly lower than in Group I. Group II theophylline plasma levels were significantly lower than those of Group I. The lower Group II theophylline levels presumably explain the reduced frequency of side effects.
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A simple, sensitive, and reproducible high-performance liquid chromatrography assay is described for the simultaneous determination of dextromethophan, dextrorphan, 3-hydroxymorphinan, and 3-methoxymorphinan in plasma and urine. A conventional solvent-solvent extraction procedure was used for the isolation of the analytes from plasma and urine samples. ⋯ The precision and accuracy were greater than 90% and the lowest detectable concentrations were 0.5 ng/ml for 3-hydroxymorphinan and 3-methoxymorphinan and 1 ng/ml for dextromethorphan and dextrophan in plasma. The utility of this method is demonstrated in a preliminary study of dextromethorphan metabolism and pharmacokinetics in man.