Inhibitory effects of propafenone on the pharmacokinetics of caffeine in humans.

Article Details

Citation

Copy to clipboard

Michaud V, Mouksassi MS, Labbe L, Belanger PM, Ferron LA, Gilbert M, Grech-Belanger O, Turgeon J

Inhibitory effects of propafenone on the pharmacokinetics of caffeine in humans.

Ther Drug Monit. 2006 Dec;28(6):779-83. doi: 10.1097/01.ftd.0000249945.64978.33.

PubMed ID

17164694 [ View in PubMed

]

Abstract

CYP1A2 is involved in the metabolism of both caffeine and propafenone, a class Ic antiarrhythmic agent. Despite the widespread consumption of caffeine, drug-drug interactions with this agent are often overlooked. This study investigated effects of propafenone on the pharmacokinetics of caffeine. Eight healthy volunteers were included in our study. A total of 300 mg of caffeine was given on 2 occasions, once alone and once during the coadministration of 300 mg propafenone. Serial blood samples were collected and pharmacokinetic parameters were estimated using a population pharmacokinetic approach. A one-compartment PK model with first-order absorption and elimination described plasma concentration profiles. Concomitant administration of propafenone decreased caffeine oral clearance from 8.3 +/- 0.9 L/h to 5.4 +/- 0.7 L/h (P < 0.05). Elimination half-life of caffeine was also increased 54% by propafenone. One of our volunteers was a poor metabolizer of CYP2D6. Concomitant administration of propafenone to this volunteer caused the greatest increase in caffeine plasma concentrations. These results support the concept of competitive inhibition between propafenone and caffeine. Our results suggest that propafenone causes significant inhibition of CYP1A2 activity leading to a decrease in the clearance of caffeine. Caffeine has intrinsic proarrhythmic effects; thus, its coadministration with an antiarrhythmic agent such as propafenone should be used with caution, especially in patients with poor CYP2D6 activity.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Propafenone	Cytochrome P450 1A2	Protein	Humans	Unknown	Substrate Inhibitor	Details