Functional and biological determinants affecting the duration of action and efficacy of anti-(+)-methamphetamine monoclonal antibodies in rats.
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.
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
Elizabeth M
EM
Laurenzana
Howard P
HP
Hendrickson
Dylan
D
Carpenter
Eric C
EC
Peterson
W Brooks
WB
Gentry
Michael
M
West
Yingni
Y
Che
F Ivy
FI
Carroll
S Michael
SM
Owens
D019969:Amphetamine-Related Disorders / Q000188:drug therapy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D003429:Cross Reactions; D007116:Immunization, Passive; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D008694:Methamphetamine