K. M. Ress

Pharmacokinetic and blood pressure effects of carvedilol in patients with chronic renal failure

SummaryThe pharmacokinetic and acute systemic haemodynamic effects of a single oral dose of 50 mg carvedilol has been studied in 24 hypertensive patients with chronic renal failure. The patients were stratified into 3 groups according to the creatinine clearance: I 51–90 ml · min−1; II 26–50 ml · min−1; III 4–25 ml · min−1.The area under plasma level time curve AUC, the elimination half-life t/12, the maximum plasma concentration Cmax, the time to peak concentration tmax were not significantly different between groups, whereas the amount of unchanged drug or metabolite excreted in urine Ae and the renal clearance CLR of carvedilol and its metabolites M2, M4, M5 were significantly decreased in Group III. Blood pressure and heart rate decreased in all 3 groups of patients after acute administration of 50 mg carvedilol. Mild adverse effects were reported in 6 patients. Despite a decrease in the renal clearance of carvedilol and of its metabolites with decreasing kidney function, its main pharmacokinetic parameters remained unchanged. The present results suggest that the dose of carvedilol need not be reduced in hypertensive patients with chronic renal failure.

Simplified, rapid and inexpensive extraction procedure for a high-performance liquid chromatographic method for determination of disopyramide and its main metabolite mono-N-dealkylated disopyramide in serum

A simplified, rapid and inexpensive extraction procedure for the determination of the antiarrhythmic drug disopyramide and its main metabolite mono-N-desalkylated disopyramide in serum by high-performance liquid chromatography has been developed. The analysis uses ultraviolet detection at 254 nm, and a 5 micron reversed-phase column with a mobile phase of water-triethylamine-acetonitrile-PIC-B8 reagent. Serum extraction is performed with dichloromethane and 1 M sodium hydroxide. p-Chlorodisopyramide is used as internal standard. Recovery rates were 94.5% (S.D. 5.7%) for disopyramide, 96.8% (S.D. 2.2%) for mono-N-desalkylated disopyramide and 97.9% (S.D. 2.8%) for the internal standard.

Renal effects of the new calcium channel blocking drug isradipine

SummaryThe acute effect of a single oral dose of isradipine 5 mg on blood pressure, renal haemodynamics, electrolyte excretion and plasma renin activity was studied in 10 healthy males.Isradipine did not produce a significant change in systolic or diastolic blood pressure, and glomerular filtration rate, renal plasma flow, renal vascular resistance, and urinary albumin excretion remained constant. There was a marked natriuretic and diuretic effect about 1–3 h after isradipine. Plasma renin activity showed a slight, insignificant increase 1 h after dosing. Uric acid clearance and β2-microglobulin excretion showed no significant changes, despite an increase in sodium clearance, suggesting an additional mechanism of action other than the proximal tubular natriuretic effect of isradipine in normotensive volunteers.

Regulation of plasma aldosterone during hemodialysis

In order to clarify the influence of serum potassium, serum sodium and plasma angiotensin II concentrations on aldosterone release during hemodialysis (HD), six chronic hemodialysis patients were studied during HD with varying dialysate sodium concentrations and different buffers. Plasma aldosterone concentrations were higher during acetate than bicarbonate HD, during low sodium compared to high sodium HD, and were correlated inversely to serum sodium concentrations. The decline in plasma aldosterone concentrations during HD paralleled the decrease in serum potassium concentrations, and plasma aldosterone concentrations were correlated with serum potassium concentrations. In addition, plasma aldosterone and plasma angiotensin II concentrations were correlated significantly. It is proposed that serum potassium and the renin-angiotensin system are the main factors of aldosterone release during hemodialysis, while serum sodium per se seems to be of less importance. The dialysate buffer employed also plays a role in aldosterone regulation (via the renin-angiotensin system)

Rapid high-performance liquid chromatographic method for the quantification of mexiletine and its metabolites in serum

The aim of this study was to develop an HPLC assay for the simultaneous determination of mexiletine hydrochloride and mexiletine metabolites. The method had to be rapid, simple and accurate in the therapeutic range and in-expensive, to allow for easy monitoring of the drug in clinical practice. Samples were obtenained from normal volonteers, from patients treated with cardiovascular drugs or with mexiletine

Rapid and inexpensive high-performance liquid chromatographic method for the quantification of flecainide in serum

Although the antiarrhythmic efficacy of flecainide acetate is not correlated directly with its serum level, the determination of the drug is recommended where drug therapy is ineffective in order to differentiate failure of therapy from suboptimal dosing, where adverse effects occur, or in order to check a patient’s compliance. The aim of this study was to develop a high-performance liquid chromato- graphic (HPLC) assay for flecainide acetate which is rapid and accurate in the therapeutic range and inexpensive, allowing easy drug monitoring in clinical practice.

Quantification of cibenzoline and its imidazole metabolite by high-performance liquid chromatography in human serum

Cibenzoline, 4,5-dihydro-Z(2,2-diphenylcyclopropyl) -lH-imidazole, is a new class 1 antiarrhythmic drug chemically not related to any other class 1 antiarrhythmic agent. The imidazole metabolite of cibenzoline, 2(2,2-diphenylcyclopropyl) -lH-imidazole (I), is almost devoid of antiarrhythmic action [ 11. The efficacy of cibenzoline has been shown by several investigators in the treatment of supraventricular and ventricular arrhythmias [ 2-7 1. Although it is generally unnecessary to determine serum levels of antiarrhythmic drugs, the determination of plasma levels is recommended in cases of side-effects, unexplained failure of drug therapy and possible drug interactions [8]. The aim of the present study was to develop a simple but accurate highperformance liquid chromatographic (HPLC) method to determine cibenzoline and its metabolite (I) in human serum.

Serum angiotensin-converting enzyme as a marker of dialyzer membrane biocompatibility?

Dr. B.K. Krämer, Medizinische Universitätsklinik, Otfried-Müller-Strasse 10, D-7400 Tübingen (FRG) Sir, We have read with interest the recent letters of Maher et al. [1] and Docci et al. [2]. Both authors suggest that serum angiotensin-converting enzyme is not a useful marker of dialysis membrane biocompatibility, in contrast to earlier findings of Nielsen et al. [3]. 16 patients on maintenance haemodialysis for 2–186 months were studied during haemodialysis with cupro-phane and non-cuprophane membranes [4]. Serum angiotensin-converting enzyme decreased slightly during haemodialysis, independent of the dialyzer membrane used. In addition, serum angiotensin-converting enzyme levels were nearly identical during use of a cuprophane and a non-cuprophane dialyzer membrane (82.3 ± 3.9 U/min/1 vs. 82.6 ± 3.3 U/min/1; range of normal values 18–40 U/min/1, corrected for haemoconcentration) [4]. Serum angiotensin-converting enzyme levels were compared with duration of maintenance haemodialysis in 23 patients (duration of maintenance haemodialysis from 2 to 216 months; age 34–78 years; etiology of renal failure: glomerulonephritis (n = 6), diabetic nephropathy (n = 5), polycystic kidney disease (n = 3), pyelonephritis (n = 2), hypertension (n = l), multiple myeloma (n = l), renal artery stenosis (n = 1), unknown (n = 4)). No significant correlation between serum angiotensin-converting enzyme and duration of maintenance haemodialysis was demonstrable (fig. 1). Our results imply that serum angiotensin-converting enzyme cannot be used as an indicator of dialyzer membrane biocompatibility and are in accordance with the results of other investigators [1, 2, 5–7]. Elevated serum angiotensin-converting enzyme levels in haemodialysis patients have also been demonstrated by several investigators [5, 6, 8–10], but have not been confirmed by others [1–3, 7, 11]. In contrast to our results, most authors were not able to demonstrate a change in serum angiotensin-