Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 1997
Comparative StudyImmunosuppressant pharmacodynamics on lymphocytes from healthy subjects and patients with chronic renal failure, nephrosis, and psoriasis: possible implications for individual therapeutic efficacy.
In organ transplantation, patients with peripheral blood mononuclear cells (PBMCs) that exhibit resistance to cyclosporine (INN, ciclosporin) or glucocorticoids in vitro are refractory to therapy based on these drugs in vivo. However, detection or distribution of the resistant patients with immunologic disorders remains to be documented. ⋯ A large subset of patients with chronic renal failure showed PBMC resistance to cyclosporine and prednisolone. Hyperresistant patients have a high risk of being refractory to immunosuppressive therapy with one of these drugs. Alternative treatment should be considered according to the individual drug-sensitivity data.
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Clin. Pharmacol. Ther. · Nov 1997
Randomized Controlled Trial Clinical TrialItraconazole increases plasma concentrations of quinidine.
Quinidine is eliminated mainly by CYP3A4-mediated metabolism. Itraconazole interacts with some but not all of the substrates of CYP3A4; it is therefore important to study the possible interaction of itraconazole with quinidine. ⋯ Itraconazole increases plasma concentrations of oral quinidine, probably by inhibiting the CYP3A4 isozyme during the first-pass and elimination phases of quinidine. The decreased renal clearance of quinidine might be the result of the inhibition of P-glycoprotein-mediated tubular secretion of quinidine by itraconazole. The concentrations of quinidine should be closely monitored if itraconazole or some other potent CYP3A inhibitors are used with quinidine.
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Clin. Pharmacol. Ther. · Aug 1997
Randomized Controlled Trial Clinical TrialIncreased toxicity of high-dose furosemide versus low-dose dopamine in the treatment of refractory congestive heart failure.
To evaluate the safety and efficacy of low-dose dopamine, high-dose furosemide, and their combination in the treatment of refractory congestive heart failure. ⋯ Combined low-dose intravenous dopamine and oral furosemide have similar efficacy but induce less renal impairment and hypokalemia than higher doses of intravenous furosemide taken either alone or with low-dose dopamine. The renal impairment induced by intravenous furosemide is probably related to its hypotensive effect in patients with refractory congestive heart failure.
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Clin. Pharmacol. Ther. · Jul 1997
Randomized Controlled Trial Clinical TrialA randomized double-blind study of carbamazepine in the treatment of cocaine abuse.
A 12-week, randomized, double-blind, placebo-controlled, fixed-dose outpatient study of carbamazepine (400 mg and 800 mg) in the treatment of cocaine dependence was performed. Data were analyzed with respect to both treatment condition and carbamazepine serum levels. ⋯ Higher serum carbamazepine levels were associated with a lower rate of positive cocaine urinalysis, fewer days of self-reported cocaine use, briefer craving episodes, and greater subject interval retention. The clinical and methodologic implications of these findings and of the study design are discussed.
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Clin. Pharmacol. Ther. · Apr 1997
Randomized Controlled Trial Clinical TrialEffect of codeine on gastrointestinal motility in relation to CYP2D6 phenotype.
Codeine is widely used as an analgesic and antitussive drug. The analgesic effect of codeine is mediated by its metabolite morphine, which is formed by the polymorphically expressed enzyme CYP2D6; therefore poor metabolizers have no analgesia after administration of codeine. Like other opiates, codeine causes a delay of gastric emptying and spastic constipation. It is not yet known whether the effect on gastrointestinal motility is mediated by codeine or its metabolite morphine. ⋯ Because the orocecal transit time prolongation after codeine administration was observed only in extensive metabolizers, the effect of codeine on gastrointestinal motility, like the analgesia, is mediated by its metabolite morphine.