Concentration-effect relation of succinylcholine chloride during propofol anesthesia.
BACKGROUND
The pharmacokinetics and pharmacodynamics of succinylcholine were studied simultaneously in anesthetized patients to understand why the drug has a rapid onset and short duration of action. A quantitative model describing the concentration-effect relation of succinylcholine was proposed. The correlation between hydrolysis in plasma and elimination was also examined.


METHODS
Before induction of anesthesia, blood was drawn for analysis in seven adults. Anesthesia was induced with propofol and remifentanil. Single twitch stimulation was applied at the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis was measured. Arterial blood was drawn frequently after succinylcholine injection to characterize the front-end kinetics. Plasma concentrations were measured by mass spectrometry, and pharmacokinetic parameters were derived using compartmental and noncompartmental approaches. Pharmacokinetic-pharmacodynamic relations were estimated.


RESULTS
The mean degradation rate constant in plasma (1.07 +/- 0.49 min(-1)) was not different from the elimination rate constant (0.97 +/- 0.30 min(-1)), and an excellent correlation (r2 = 0.94) was observed. Total body clearance derived using noncompartmental (37 +/- 7 ml x min(-1) x kg(-1)) and compartmental (37 +/- 9 ml x min(-1) x kg(-1)) approaches were similar. The plasma-effect compartment equilibration rate constant (k(eo)) was 0.058 +/- 0.026 min(-1), and the effect compartment concentration at 50% block was 734 +/- 211 ng/ml.


CONCLUSIONS
Succinylcholine is a low-potency drug with a very fast clearance that equilibrates relatively slowly with the effect compartment. Its disappearance is greatly accountable by a rapid hydrolysis in plasma.
Roy
Julie J
JJ
Faculté de Pharmacie, Département d'Anesthésiologie, Université de Montréal, Québec, Canada.
Donati
François
F
Boismenu
Daniel
D
Varin
France
F
D000328:Adult; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D013390:Succinylcholine / Q000493:pharmacokinetics* / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D009467:Neuromuscular Depolarizing Agents; D013390:Succinylcholine; D015742:Propofol