Coffee and Tobacco Interactions with Lamotrigine
Abstract number :
2.209
Submission category :
7. Antiepileptic Drugs / 7D. Drug Interaction
Year :
2016
Submission ID :
196785
Source :
www.aesnet.org
Presentation date :
12/4/2016 12:00:00 AM
Published date :
Nov 21, 2016, 18:00 PM
Authors :
Timothy Welty, Drake University, Des Moines; Barry E. Gidal, University of Wisconsin, Madison, Wisconsin; Michael Privitera, University of Cincinnati; Michel J. Berg, University of Rochester; Francisco Diaz, University of Kansas Medical Center; and Ron Kr
Rationale: Lamotrigine (LTG ) is primarily metabolized by glucuronyl transferases (UGT). The major metabolite, N2-glucuronidated-LTG is inactive and the primary metabolite found in the urine. The conversion of LTG to the N2-glucuronide conjugate is via UGT1A4, although UGT1A1, 1A3, 1A6, 1A7, and UGT2B7 contribute to forming this metabolite to a lesser extent. LTG is also reportedly a substrate for several efflux transport proteins, including P-glycoprotein (PgP) and breast cancer resistance protein (BCRP). The effects of concomitant UGT inducers such as carbamazepine, phenytoin and phenobarbital on LTG PK are well known, the impact of non-drug substances such as tobacco and coffee are less clear. Literature suggests various phenolic phytochemicals contained in coffee can induce UGT expression, as well as BCRP. Cigarette smoking may also increase UGT expression in rodents, and in one report, to reduce LTG serum concentrations in patients. As a result of these reports, we qualitatively documented use of coffee and tobacco in the Equigen chronic dose study. The Equigen chronic dose study was a study of generic LTG substitution using a 4-period replicate design with 19 LTG concentrations measured over 12-hours in each subject for each period. This analysis was designed to determine if interactions were detected in this group of patients. Methods: As part of the statistical analysis of factors influencing LTG pharmacokinetics (PK) in the Equigen chronic dose study, we collected qualitative data from enrolled patients on their use of coffee and tobacco. Subjects were instructed to not change their typical consumption of these products for the duration of the study. Statistical analysis of these factors was done prospectively. Results: A total of 35 subjects dose were included in the analysis. No significant difference was seen in PK parameters with any of the products. Conclusions: Coffee and tobacco use did not alter PK parameters of lamotrigine. Funding: US Food and Drug Administration (contract HHSF223201110112A) Epilepsy Foundation American Epilepsy Society
Antiepileptic Drugs