Tissue Distribution of Exogenously Administered Human Serum Butyrylcholinesterase-Soman Conjugate(HuBuChE-GD) in Guinea Pigs to Predict its Toxicity
Abstract
I.m. injection of HuBuChE is the only applicable method for enzyme administration under operational conditions. Pharmacokinetic studies in guinea pigs revealed that the Cmax of the enzyme was reached at 24 h after administration of the enzyme. At that time approx. 30% of the amount of administered enzyme was present in blood. It is still unknown whether the remainder of the enzyme is available in the tissues, which may explain the protective ratios found in earlier studies. In this bioavailability study the distribution of HuBuChE was examined after i.v. injection (100 % bioavailability) and i.m. administration. The enzyme was inhibited with 14C-soman, which facilitated the study of the distribution of only exogenous HuBuChE. At 24 h after i.v. administration of HuBuChE, 43 % of the administered amount was present in blood, while 33% of the administered amount was present in blood after i.m. administration. The increase of the HuBuChE concentration in richly perfused organs was rather low and accounted for less than 1 % for each organ to the total recovery. The recovery in intestines was rather high (5-8%), which might indicate that the exogenous enzyme was excreted in the feces. For pegylated HuBuChE, the recovery in blood at 24 h was 36 % after i.v. administration and only 17 % after i.m. administration. The increase of the concentration of pegylated HuBuChE in the tissues was also rather low. The contribution of each organ to the total recovery was less than 1%. The recovery of radioactivity in the intestines ranged between 2-6% of the administered amount, which directs to excretion of the enzyme.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2010
- Accession Number
- ADA524175
Entities
People
- M.j. Vander Schans