Ajmaline test in a patient with chronic renal failure. A pharmacokinetic and pharmacodynamic study.
Pharmacokinetic and pharmacodynamic properties were studied after intravenous administration of ajmaline 1 mg/kg in an anuric patient, who underwent the electrophysiological ajmaline test. The magnitude and rate of onset of the typical electrophysiological effects of ajmaline (prolongation in atrio-Hisian and His-ventriculum conduction times) were within the range of normal values. The plasma concentration curve showed a triexponential decay with half-lives as follows: initial phase (t1/2 alpha) 1.34 min, fast elimination phase (t1/2 beta) 10.13 min and terminal (slow) phase (t1/2 gamma) 258.6 min. Other relevant pharmacokinetic parameters calculated were: total plasma clearance 45.91 L/h; volume of distribution 285.6L; protein binding 47%. Five hours after administration the patient underwent a 3.5h haemodialysis without any substantial increase in the slope of the final elimination phase of the curve. A major problem in interpreting the pharmacokinetic results is the lack of reliable reference data in healthy subjects. It is likely that the ajmaline t1/2 reported in the literature (13.4 min) does not reflect the true terminal t1/2 of the drug, because it was determined during an unduly short sampling period (30 min). Nevertheless, if we compare just the first 30 min of the concentration-time curves, our results are nearly superimposable on those found in healthy subjects.
Padrini
R
R
Department of Pharmacology, University of Padua, Italy.
Compostella
L
L
Piovan
D
D
Javarnaro
A
A
Cucchini
F
F
Ferrari
M
M
D000368:Aged; D000404:Ajmaline / Q000493:pharmacokinetics / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006327:Heart Block / Q000150:complications / Q000175:diagnosis*; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*
D000404:Ajmaline