title: Modafinil influences the pharmacokinetics of intravenous cocaine in healthy cocaine-dependent volunteers.
abstract: OBJECTIVE
  To determine if modafinil, a putative treatment for cocaine dependence, influences the pharmacokinetics of intravenous cocaine in otherwise healthy cocaine-dependent volunteers.
  
  
  METHODS
  Cocaine 20 or 40 mg was administered intravenously on consecutive days over 1 minute at baseline and after modafinil administration at each of two dosages of 400 and 800 mg/day for 7 days.
  
  
  RESULTS
  Twelve subjects completed the clinical protocol. Compared with baseline, the cocaine peak plasma concentration was decreased after both the 20 and 40 mg cocaine infusions, but the reduction was only statistically significant after the 40 mg cocaine infusion (p < 0.01 after modafinil 400 mg/day; p < 0.05 after modafinil 800 mg/day). The area under the cocaine plasma concentration-time curve from 0 to 180 minutes (AUC180) was significantly decreased by modafinil administration (p < 0.01 and p < 0.001 for modafinil 400 and 800 mg/day, respectively, for the cocaine 20mg dose; p < 0.001 for the cocaine 40 mg dose at both modafinil levels). There were no significant changes in total AUC, clearance or elimination half-life of cocaine.
  
  
  CONCLUSIONS
  This study did not find evidence for a harmful pharmacokinetic interaction between modafinil and cocaine. In contrast, long-term administration of modafinil significantly decreased systemic exposure to cocaine during the first 180 minutes following intravenous cocaine administration.
authors.affiliation: Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (MUSC), Charleston, South Carolina, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Donovan
authors.forename: C Lindsay
authors.initials: CL
authors.lastname: DeVane
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Malcolm
authors.forename: Jurij
authors.initials: J
authors.lastname: Mojsiak
authors.forename: C Nora
authors.initials: CN
authors.lastname: Chiang
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elkashef
authors.forename: Robin M
authors.initials: RM
authors.lastname: Taylor
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D018579:Patient Selection; D016037:Single-Blind Method
chemical_list: D000779:Anesthetics, Local; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D003042:Cocaine; D000077408:Modafinil