Intramuscular atropine in healthy volunteers: a pharmacokinetic and pharmacodynamic study.
In a randomized, double-blind, placebo controlled crossover study, the pharmacokinetics and some clinically important pharmacodynamic effects of intramuscular atropine (dl-hyoscyamine) were studied in 6 healthy male volunteers. The plasma concentrations of l-hyoscyamine were analyzed by radioreceptor assay (RRA) and the plasma concentrations of dl-hyoscyamine by radioimmunoassay (RIA). The absorption rate and the elimination rate of dl-hyoscyamine and l-hyoscyamine were comparable (tmax = 8.40 vs 8.67 min, t1/2el = 2.95 vs 2.43 h, dose 0.02 mg/kg) but the mean maximum plasma concentration of dl-hyoscyamine was 2.9 times and the mean AUC value 6.0 times higher than that of l-hyoscyamine which indicates a kinetic difference between the enantiomers. The concentrations of d-hyoscyamine calculated from the dl- and l-hyoscyamine concentrations reached maximum between 1 and 2 h after drug injection. The renal excretion of l-hyoscyamine occurred mostly in 6 h (34% of the dose) and no conjugated drug forms were detected. The increase in heart rate was observed only after the higher dose (0.02 mg/kg) and it was significant between 30 min and 2 h. The plasma concentrations of l-hyoscyamine and the change in heart rate expressed as percentages showed a linear correlation: concentrations under 0.5 micrograms/l caused slowing of rate, higher concentrations caused acceleration. Also, the antisialagogue effect (30 min-3 h) correlated with plasma concentrations.
Kentala
E
E
Department of Anesthesiology, University of Turku, Finland.
Kaila
T
T
Iisalo
E
E
Kanto
J
J
D000328:Adult; D001285:Atropine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000652:urine; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D013997:Time Factors
D001285:Atropine