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Functional and biological determinants affecting the duration of action and efficacy of anti-(+)-methamphetamine monoclonal antibodies in rats.
- Source :
-
Vaccine [Vaccine] 2009 Nov 23; Vol. 27 (50), pp. 7011-20. Date of Electronic Publication: 2009 Oct 01. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Amphetamine-Related Disorders drug therapy
Animals
Antibodies, Monoclonal immunology
Antibodies, Monoclonal therapeutic use
Brain metabolism
Cross Reactions
Immunization, Passive
Male
Methamphetamine blood
Methamphetamine immunology
Rats
Rats, Sprague-Dawley
Antibodies, Monoclonal pharmacokinetics
Methamphetamine antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2518
- Volume :
- 27
- Issue :
- 50
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 19800446
- Full Text :
- https://doi.org/10.1016/j.vaccine.2009.09.072