期刊
CLINICAL PHARMACOKINETICS
卷 44, 期 7, 页码 753-765出版社
ADIS INT LTD
DOI: 10.2165/00003088-200544070-00006
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资金
- NCRR NIH HHS [M01 RR01070-18] Funding Source: Medline
- NIDA NIH HHS [N01 DA-98102] Funding Source: Medline
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR001070] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [N01DA098102] Funding Source: NIH RePORTER
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 40mg 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 40mg cocaine infusions, but the reduction was only statistically significant after the 40mg 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 (AUC(180)) 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 40mg dose at both modafinil levels). There were no significant changes in total AUC, clearance or elimination half-life of cocaine. Conclusion: 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.
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