Pharmacokinetic and Functional Properties of Anti‐Methamphetamine Monoclonal Antibodies

Previous pharmacological studies suggest time‐dependent decreases in the function of anti‐methamphetamine monoclonal antibodies (anti‐METH mAb). We hypothesized that differences in mAb binding properties and/or mAb pharmacokinetics (PCKN) could cause these changes. We first conducted in vitro studies of mAb affinities in serum compared with buffer. Equilibrium dialysis revealed no significant differences between serum and buffer K D values for 4 of our anti‐METH mAb. In rat PCKN studies, the 4 anti‐METH mAb tested had elimination half‐lives of ~7 days, suggesting no differences. Next, we determined the impact of 6 different anti‐METH mAb on METH PCKN in rats. Initially, all mAb caused significant increases in METH serum concentrations, with the highest affinity mAb6H4 (K D = 10 nM) causing a ~80‐fold increase; however, this was not maintained during the 2 week study. Only mAb4G9 (K D = 34 nM) maintained high METH binding in serum throughout the study. The effect of mAb4G9 and mAb6H4 on METH serum and brain concentrations immediately after mAb treatment was then determined. Both mAb significantly increased METH serum levels (>70‐fold) and decreased brain METH levels (>2‐fold); however, the mAb4G9 had more dramatic effects over time than mAb6H4. These studies suggest that while mAb4G9 maintained function, most of the anti‐METH mAb are partially inactivated in vivo . (Supported by P01 DA14361 and R01DA11560).