Pharmacokinetics of physostigmine after intravenous, intramuscular and subcutaneous administration in surgical patients.

Abstract

The pharmacokinetics of physostigmine after intravenous, intramuscular or subcutaneous administration as well as its arousal effect after anaesthesia have been studied in surgical patients in the early postoperative period. After intravenous administration physostigmine had a very rapid plasma elimination with a plasma clearance ranging from 47 to 163 l/h with a mean +/- s.d. of 92.5 +/- 37.7 l/h. The volume of distribution was 46.5 +/- 19.2 l, while distribution and plasma elimination half-lives were 2.3 and 22 min, respectively. A fraction of the dose was probably hydrolyzed in blood since its blood elimination half-life in vitro was approximately 190 min. After both intramuscular and subcutaneous administration the systemic availability was almost complete, the plasma terminal half-lives only being somewhat longer than after intravenous administration. Plasma clearance, volume of distribution and elimination half-life of physostigmine were not correlated to age or body weight of the patients. The rapid plasma clearance of physostigmine resulted in a short duration of antisedative effect. After administration of 1 mg physostigmine salicylate i.v., drug-induced sedation was rapidly reversed with a duration of 30-60 min. The duration of action was similar after intramuscular injection but onset was delayed by 20-30 min. It was concluded that a plasma concentration of 3-5 ng/ml of physostigmine should be exceeded if an adequate analeptic effect is to be achieved, meaning that 2 mg of physostigmine had to be administered subcutaneously in order to achieve a satisfactory reversal of sedation. The short duration of action may hamper the use of physostigmine as an agent for reversal of drug-induced sedation and anticholinergic effects after surgery.