Application of a new radiometric high-performance liquid chromatographic assay to define physostigmine pharmacokinetics in guinea pigs.
A sensitive high-performance liquid chromatographic method was developed to determine pharmacokinetic parameters of [3H]physostigmine from serial plasma samples from guinea pigs. Physostigmine was totally resolved from its metabolite, eseroline. The limit of sensitivity was 0.05 ng/ml from 0.2 ml plasma. Extraction efficiency was 99.6%. Within-run and among-run coefficients of variation (n = 6) for 0.2, 0.75, 1.5 and 2.5 ng/ml [3H]physostigmine ranged from 0.7 to 20% and 16 to 32%, respectively. Physostigmine (5 micrograms/kg) intramuscularly administered to the guinea pig (n = 6) reached maximum serum concentration (1.5 ng/ml) in 26 min. The apparent volume of distribution and systemic clearance were 1.4 l/kg and 26 ml/min/kg, respectively. This method was successful in defining physostigmine pharmacokinetic parameters in guinea pigs and can be employed for other small animal pharmacokinetic studies.
United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
B J
BJ
Lukey
D D
DD
Marlow
C R
CR
Clark
M P
MP
McCluskey
C N
CN
Lieske
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006168:Guinea Pigs; D010830:Physostigmine / Q000097:blood / Q000493:pharmacokinetics*; D011874:Radiometry
D001798:Blood Proteins; D010830:Physostigmine