Pharmacokinetic Mechanisms for Obtaining High Renal Coelimination of Phencyclidine and a Monoclonal Antiphencyclidine Antigen-Binding Fragment of Immunoglobulin G in the Rat

摘要: Our purpose was to determine mechanisms and methods for significantly increasing the renal coelimination of phencyclidine (PCP) an anti-PCP monoclonal antibody binding fragment (anti-PCP Fab). To accomplish this goal, we performed a series experiments examine dose-dependence Fab elimination, enhancing PCP urinary antigenicity repeated administration. The results showed that elimination linear over 30-fold range doses. Anti-PCP serum pharmacokinetics were best described using bi- or tri-exponential curves with terminal half-life approximately 8 hr. Nevertheless, under all experimental conditions early, nonterminal phase(s) responsible majority (60%) intact only 40% eliminated during phase. These data suggest early rapid decline in concentrations primarily due passive filtration excretion Fab, not extravascular distribution as previously described. In comparison PCP, systemic alkalinization produced significant increase 69% dose 41% recovered urine. Finally, studies administration no immune response impairment. Overall, these careful attention physiological status kidney time periods is essential maximum bound chemicals.