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.
Lukey
B J
BJ
United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Marlow
D D
DD
Clark
C R
CR
McCluskey
M P
MP
Lieske
C N
CN
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