title: Kinetic and cardiovascular effects of acute topiramate dosing among non-treatment-seeking, methamphetamine-dependent individuals.
abstract: Previously, we have shown that orally administered topiramate, a sulfamate-substituted fructopyranose derivative, appears to accentuate rather than diminish some aspects of methamphetamine-induced positive subjective mood and cognitive performance. One possible mechanism by which this might occur would be for topiramate to increase plasma methamphetamine level. Such an effect also would be expected to enhance methamphetamine-induced hemodynamic response. We, therefore, studied -- in the same experiment from which the previous findings originated -- the effects of topiramate on the kinetic profile and hemodynamic response to methamphetamine. In a 27-day inpatient study, 10 methamphetamine-dependent individuals participated in a double-blind, placebo-controlled, cross-over design, with oral doses of topiramate (0, 100, and 200 mg) administered as a pretreatment before intravenous doses of methamphetamine (0, 15, and 30 mg). The 3x3 factorial combination of topiramate and methamphetamine resulted in a sequence of the nine treatments administered to each subject in an order determined by a 9x9 Latin Square design. Methamphetamine alone was associated with prototypical increases in hemodynamic response that were not altered in the presence of topiramate. While there was no significant kinetic interaction between topiramate and methamphetamine, there was a non-significant trend for topiramate to increase plasma methamphetamine level. No significant adverse events were reported. The combination of topiramate and methamphetamine at pharmacologically relevant doses appears to be safe. Larger laboratory studies with chronic dosing regimens are needed to establish whether or not there is a kinetic interaction between topiramate and methamphetamine.
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, P.O. Box 800623, Charlottesville, VA 22908-0623, USA. bankolejohnson@virginia.edu
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.forename: Lynda T
authors.initials: LT
authors.lastname: Wells
authors.forename: John D
authors.initials: JD
authors.lastname: Roache
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wallace
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dawes
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Xin-Qun
authors.initials: XQ
authors.lastname: Wang
authors.forename: Martin A
authors.initials: MA
authors.lastname: Javors
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000503:physiopathology / Q000517:prevention & control*; D019540:Area Under Curve; D002319:Cardiovascular System / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013997:Time Factors; D000077236:Topiramate
chemical_list: D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose; D008694:Methamphetamine