Modafinil influences the pharmacokinetics of intravenous cocaine in healthy cocaine-dependent volunteers.
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.
Donovan
Jennifer L
JL
Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (MUSC), Charleston, South Carolina, USA.
DeVane
C Lindsay
CL
Malcolm
Robert J
RJ
Mojsiak
Jurij
J
Chiang
C Nora
CN
Elkashef
Ahmed
A
Taylor
Robin M
RM
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
D000779:Anesthetics, Local; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D003042:Cocaine; D000077408:Modafinil