Bupoprion may increase bioavailability of the second-generation beta receptor antagonist carvedilol, suggests a recent study reported in rats (M.B. Abrudan and colleagues, Pharmacology 99(3-4):139-143, 2017).
The authors measured or calculated pharmacokinetic parameters of a single dose of carvedilol in groups of rats pretreated with placebo or bupropion, and found an exposure to carvedilol higher in rats exposed to bupropion. How much higher is equivocal in the authors’ exposition, wherein carvedilol is reported to have increased by 180 percent (which would be a near three-fold increase, relative to placebo), while leaving unclear whether they meant that final carvedilol concentrations were 180 percent those of placebo co-treated rats after the final injection of carvedilol (nearly a two-fold increase). Carvedilol exposure was expressed in a conventional manner (area under the time-concentration curve after injection on the final day of a course of bupropion that had reached stead state blood concentration).
Whichever was meant by the authors about the degree of increase of carvedilol exposure, the putative pharmacokinetic interaction between carvedilol and bupropion (still among the most extensively used “tactical drugs” for eliciting antidepressant response when added to other antidepressants that have proved insufficiently effective for depressive syndromes) will be monitored expectantly by the authors when it arises (or not) from data-mined European medical registries or pharmacy prescription databases. (Obiter: The authors published similar findings (about increased carvedilol exposure) after repeated doses of citalopram in the next issue of the same journal (M.B. Abrudan and colleagues, Pharmacology 100(5-6):301-307, 2017), wherein they speculate that pharmacokinetic interactivity between carvedilol and citalopram devolves from inhibition by the latter of CYP2D6 (of which carvedilol is a substrate). Yet, while bupropion has been reported a potent inhibitor of CYP2D6, citalopram has been reported to be a weak inhibitor of CYP2D6, raising a possibility that the interactivity reported by the authors may be occurring by dint of a different mechanism, perhaps one in which the relevant entity is not a cytochrome P450 enzyme, but rather one of an increasingly reported group of pharmacokinetic interactions suspected to occur by dint of inhibition of membrane efflux transporters, such as para-glycoprotein, whose activity some other investigations have found correlated to that of the metabolic cytochrome enzymes implicated in a preponderance of interactions involving psychotropic drugs.