Journal
VACCINE
Volume 27, Issue 50, Pages 7011-7020Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2009.09.072
Keywords
Monoclonal antibody; Passive immunization; Methamphetamine; Pharmacokinetics; Rat
Categories
Funding
- National Institute on Drug Abuse [R01 DA1 1560, P01 DAI 4361, F32 DA018039, R01 DA05477]
- Arkansas Biosciences Institute
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These studies examined the in vivo pharmacokinetics and efficacy of five anti-methamphetamine monoclonal antibodies (mAbs, K-D values from 11 to 250 nM) in rats. While no substantive differences in mAb systemic clearance (t(1/2) = 6.1-6.9 days) were found, in vivo function was significantly reduced within 1-3 days for four of the five mAbs. Only mAb4G9 was capable of prolonged efficacy, as judged by prolonged high methamphetamine serum concentrations. MAb4G9 also maintained high amphetamine serum concentrations, along with reductions in methamphetamine and amphetamine brain concentrations, indicating neuroprotection. The combination of broad specificity for methamphetamine-like drugs, high affinity, and prolonged action in vivo suggests mAb4G9 is a potentially efficacious medication for treating human methamphetamine-related medical diseases. (C) 2009 Elsevier Ltd. All rights reserved.
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