Pharmacokinetics and immunologic consequences of repeated administrations of purified heterologous and homologous butyrylcholinesterase in mice

Aim: To assess the consequences of repeated administrations of purified human serum butyrylcholinesterase (Hu BChE) and mouse serum (Mo) BChE into mice. Main methods: Purified Hu BChE and Mo BChE isolated from the sera of CD-1 mice were administered into Balb/c or CD-1 mice. The enzymes were delivered by i.m. injections of similar to 100 U (0.15 mg) on day I and on day 28, respectively. The effects of two injections were monitored by following blood BChE and anti-BChE IgG levels. Key findings: Hu BChE displayed a mean residence time (MRT) of 50 h, and an area under the curve (AUC) of 1220 U/ml . h in Balb/c or CD-1 mice. Mo BChE exhibited an MRT of 78 h and an AUC of 1815 U/ml . h in Balb/c mice; the AUC increased to 2504 U/ml . h in CD-1 mice. A second injection of Hu BChE in both strains exhibited a marked reduction in circulatory stability. The circulatory stability of the second injection of Mo BChE was reduced in Balb/c mice, but was almost identical to the first injection in CD-1 mice. Consistent with these observations, circulating anti-BChE IgGs were observed in mice injected with Hu BChE; low levels of anti-BChE IgGs were observed only in Balb/c mice injected with Mo BChE. No antibody response was detected in CD-1 mice following either injection of homologous Mo BChE. Significance: The identical pharmacokinetic profiles and the absence of an immunologic response following a second administration of homologous BChE support the development of Hu BChE as a detoxifying drug in humans. (C) 2009 Published by Elsevier Inc.