Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Nov 1998
Randomized Controlled Trial Clinical TrialMetabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: an interaction study with fluvoxamine and ketoconazole as in vivo inhibitors.
Potential drug-drug interactions can be identified in vitro by exploring the importance of specific cytochrome P450 (CYP) isozymes for drug metabolism. The metabolism of the local anesthetic ropivacaine to 3-hydroxyropivacaine and (S)-2',6'-pipecoloxylidide was shown in vitro to be dependent on CYP1A2 and 3A4, respectively. In this in vivo model study we quantitated the role of these 2 isozymes for the metabolism of ropivacaine. ⋯ CYP1A2 is the most important isozyme for the metabolism of ropivacaine. Drug-drug interactions with strong inhibitors of this isozyme could be of clinical relevance during repeated administration. A potent inhibitor of CYP3A4 causes a minor decrease in clearance, which should be of no clinical relevance.
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Clin. Pharmacol. Ther. · Nov 1998
Randomized Controlled Trial Clinical TrialCatecholamines and heart function in heart transplant patients: effects of beta1- versus nonselective beta-blockade.
To evaluate cardiac responses to norepinephrine and epinephrine in heart transplant patients compared with patients with mild essential hypertension and to evaluate the contribution of beta2-receptors versus beta1-receptors to the cardiac responses by assessing the effects of the 2 agonists after treatment with placebo compared with the beta1-selective blocker atenolol and the nonselective blocker nadolol. ⋯ Both absence of parasympathetic buffering and diminished systemic clearance contributed to the enhanced cardiac responses to infusion of norepinephrine and epinephrine in heart transplant patients compared with patients with essential hypertension. Cardiac beta2-receptors mediate most of the chronotropic and inotropic responses to epinephrine in both patients with hypertension and heart transplant patients.