Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Oct 1996
Comparative Study Clinical Trial Controlled Clinical TrialAnalysis of the variability in the pharmacokinetics and pharmacodynamics of bumetanide in critically ill infants.
Account for the interindividual variability in the pharmacokinetics and pharmacodynamics of bumetanide after intravenous administration of single doses to critically ill infants. ⋯ The pharmacokinetics of bumetanide were influenced significantly by age and disease. Differences in pharmacokinetics between patients with lung and heart disease were primarily due to differences in total clearance. The administered dose of bumetanide and age were positive determinants of bumetanide excretion rate and pharmacodynamic responses. Pharmacodynamic responses as a function of bumetanide excretion rate were not significantly different between disease groups.
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Clin. Pharmacol. Ther. · Oct 1996
Randomized Controlled Trial Clinical TrialDetermination of cytochrome P450 3A4/5 activity in vivo with dextromethorphan N-demethylation.
Dextromethorphan is used widely in vivo to phenotype the polymorphically expressed cytochrome P450 (CYP) 2D6. Dextromethorphan is N-demethylated in vitro to 3-methoxymorphinan by human CYP3A4/5. We examined whether the dextromethorphan/3-methoxymorphinan urinary metabolic ratio (MR) could be used as an in vivo probe of CYP3A. ⋯ The changes in CYP3A activity were independent of CYP2D6 phenotype and were also observed after 24- and 48-hour urine collections in extensive metabolizers and poor metabolizers. In addition, MRs reflecting CYP2D6 and CYP3A were not significantly correlated. We conclude that the commonly used antitussive dextromethorphan can be used as an in vivo marker of CYP3A and CYP2D6 activity.
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Clin. Pharmacol. Ther. · Oct 1996
Clinical Trial Controlled Clinical TrialDose-ranging evaluation of bumetanide pharmacodynamics in critically ill infants.
Determine the diuretic effects of single intravenous doses of bumetanide in volume-overloaded critically ill infants. ⋯ Maximal diuretic responses occurred at a bumetanide excretion rate of about 7 micrograms/kg/hr, corresponding to doses of 0.035 to 0.040 mg/kg. Higher doses produced a proportionately higher bumetanide excretion rate but no increased diuretic effect. Lower doses of bumetanide had the greatest diuretic efficiency, suggesting that continuous infusion of low doses of bumetanide or intermittent low-dose boluses may produce optimal diuretic responses in critically ill infants.