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© 1986 Oxford University Press

research-article

Distribution and Pharmacokinetics of Physostigmine in Rat after Intramuscular Administration1

SATU M. SOMANI and ABDUL KHALIQUE

Department of Pharmacology. Southern Illinois University School of Medicine P.O. Box 3926, Springfield, Illinois 62708

Distribution and Pharmacokinetics of Physostigmine in Rat after Intramuscular Administration. SOMANI, S. M. AND KHALIQUE, A. (1986). Fundam Appl. Toxicol. 6, 327–334. The distribution and pharmacokinetics of [3H]physostigmine (Phy) and the relationship between the time course of Phy concentration and butyrylcholinesterase (BuChE) inhibition in plasma was studied in rat after im administration (650 µg/kg). The concentrations of Phy and its metabolites were determined in plasma and brain by high-performance liquid chromatography and by counting the radioactivity in the chromatographic fractions. The half-life of Phy in plasma and brain was 17 and 16 min, respectively. The brain-to-plasma ratio of Phy peaked (1.61) at 22 min. The time course of Phy and its metabolites (eseroline, M1 and M2 indicated that Phy was rapidly metabolized and M1 appeared to be the major metabolite. The distribution studies showed that the concentration of radioactivity per gram of tissue was higher in kidney and liver than the other tissues. The time course of BuChE activity and plasma Phy concentration showed that the maximum enzymatic inhibition (47%) occurred at about the same time (7 min) as the peak plasma concentration (583 ng/ml at 5 min). The enzymatic activity recovered to 81% at 2 hr and 100% within 24 hr.


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