Ajmaline Test in a Patient with Chronic Renal Failure

Abstract

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.

Pharmacokinetics and Electrophysiological Effects of Intravenous Ajmaline

“…Recently, we studied the pharmacokinetics of ajmaline in an anuric patient undergoing periodic haemodialysis (Padrini et al 1991) and the values of total body clearance and terminal half-life found (17.00 mllmin/kg and 4.3 hours, respectively) were within the range reported here (CL 6.30 to 17.27 mllmin/kg; t\l214.6 to 16.5 hours). This confirms the minimal role played by the kidney in ajmaline elimination.…”

“…However, our results have shown that, in a group of patients who underwent the ajmaline test because of suspected paroxysmal AV block, the t\l21 of the drug averaged 7.3 hours. As discussed in a previous paper (Padrini et al 1991), such a discrepancy might be attributed to the less sensitive assay methods used in the past, which did not permit plasma concentration decay to be followed for long enough to detect the true elimination phase.…”

“…We have described the pharmacokinetic behaviour of ajmaline in a patient with chronic renal failure receiving haemodialysis (Padrini et al 1991). However, due to the· lack of reliable data in healthy volunteers, we could not draw firm conclusions about the possible consequences of renal failure on ajmaline pharmacokinetics.…”

“…The coefficient of variation within a series of spiked plasma samples was 2.3% at a concentration of 0.1 mgIL and the minimum detectable concentration was"" 1 J.lg/L. The unbound fraction of the drug in plasma was evaluated using the equilibrium dialysis technique (Padrini et al 1991). Plasma (lml) adjusted to pH 7.4 with 0.3 mollL phosphoric acid was dialysed against Iml of 0.13 mollL phosphate buffer for 4 hours at 37°C (,Dianorm' apparatus, cellulose membranes with 5000D molecular weight cut-off).…”