Sensitive method for the determination of the antiarrhythmic drug detajmium in serum by solid-phase extraction and high-performance liquid chromatography with fluorimetric detection.

The objective of this study was to develop a very sensitive and selective method for the determination of detajmium (4-3-diethylamino-2-hydroxypropyl-ajmaline), a sodium-channel-blocking drug with antiarrhythmic properties, in serum. A high-performance liquid chromatography (HPLC) method with solid-phase extraction and fluorimetric detection has been applied. Serum samples were diluted with phosphate buffer (pH 3.

Histamine response and local cooling in the human skin: involvement of H1- and H2-receptors.

Aims: Histamine may contribute locally to cutaneous blood flow control under normal and pathologic conditions. The objective of this study was to observe the influence of skin temperature on histamine vasodilation, and the roles of H1-and H2-receptors using novel noninvasive methods.

Methods: Eleven healthy subjects received, double-blind, single doses of the H1-receptor antagonist cetirizine (10 mg), cetirizine (10 mg) plus the H2-receptor antagonist cimetidine (400 mg), or placebo on separate occasions.

Regional drug information service.

Background: Drug information centers (DICs) were established in Europe more than two decades ago. The majority of German DICs were created in the 90s. The regional University hospital-based DIC, which offers services to physicans, is now in operation for three and a half years .

Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans.

Purpose: To quantitate the effect of verapamil administered orally, a calcium channel blocker and potent inhibitor of P-glycoprotein on oral pharmacokinetics of the beta1-adrenergic receptor antagonist talinolol, a substrate of P-glycoprotein.

Subjects And Methods: In a randomized, crossover placebo-controlled study, oral pharmacokinetics of talinolol (50 mg) after concomitant administration of single doses of R-verapamil (120 mg) or placebo were investigated in 9 healthy volunteers. Concentrations of talinolol, verapamil, and its main metabolite norverapamil were measured in serum with HPLC.

Pharmacokinetics and safety of propiverine in patients with fatty liver disease.

Objective: The present study was designed to assess the pharmacokinetics of propiverine after single and multiple dosing in patients with and without fatty liver disease.

Methods: The serum concentration-time curves of propiverine and its main metabolite propiverine-N-oxide were investigated in 12 patients with mild to moderate impairment of liver function (mean antipyrine clearance 26.0 ml x min(-1)) and in 12 controls (antipyrine clearance 42.

Scopolamine model of dementia: electroencephalogram findings and cognitive performance.

Background: Memory and cognitive functions are known to decline with advancing age. Studies have suggested that this may be due to a decrease in cholinergic function in the brains of elderly people. This review aims to assess studies documented in the literature dealing with the 'scopolamine model' of dementia.

Effects of digoxin and digitoxin on circadian blood pressure profile in healthy volunteers.

Background: The aim of the study was to investigate the potential effects of chronic digoxin or digitoxin treatment or circadian blood pressure profile in normotensive subjects.

Methods: In two randomized double-blind, placebo-controlled cross-over protocols, 22 healthy normotensive subjects were enrolled, 12 subjects in either study. After adequate loading doses, digoxin 0.

Amiodarone causes endothelium-dependent vasodilation in human hand veins in vivo.

Objective: Amiodarone, a class III antiarrhythmic agent, is a potent coronary vasodilator. However, direct evidence for its vasodilatory effects in human vasculature in vivo is not available. The aim of the study was to investigate the short-term effects of amiodarone in preconstricted human hand veins and to explore the underlying mechanisms.

Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration.

The effects of subcutaneously administered scopolamine on quantitative electroencephalogram (qEEG) and cognitive performance were evaluated and correlated with pharmacokinetic parameters in a randomized, double-blind placebo-controlled crossover study of 10 healthy male volunteers. Changes in qEEG and cognition were determined for 8 hours after drug administration. Scopolamine produced dose- and time-dependent impairments of attention and memory and a time-dependent increase in delta power (1.

Pharmacokinetics and safety of candesartan cilexetil in subjects with normal and impaired liver function.

Objective: The influence of liver disease on the pharmacokinetics of candesartan, a long-acting selective AT1 subtype angiotensin II receptor antagonist was studied.

Methods: Twelve healthy subjects and 12 patients with mild to moderate liver impairment received a single oral dose of 12 mg of candesartan cilexetil on day 1 and once-daily doses of 12 mg on days 3-7. The drug was taken before breakfast.

[Sicca symptoms and hearing loss in Behçet's syndrome].

History And Admission Findings: A 39-year-old woman sustained an irreversible hearing loss in the left ear, followed 6 months later by a left facial paresis. Oral aphthous ulcers frequently recurred with fever of up to 39.5 degrees C.

Pharmacokinetics of imidapril and its active metabolite imidaprilat following single dose and during steady state in patients with chronic renal failure.

Objective: An open study on the single dose and steady-state pharmacokinetics of imidapril, a novel prodrug-type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite imidaprilat was conducted in eight patients with moderate chronic renal failure [mean creatinine clearance (CL(CR)) 64 ml x min(-1); range 42-77 ml x min(-1)], eight patients with severe chronic renal failure (mean CL(CR), 18 ml x min(-1); range 11-29 ml x min(-1)) and eight healthy volunteers with normal renal function. Subjects received an oral dose of 10 mg imidapril once per day for 7 days.

Results: No statistical differences of either maximum concentration (Cmax) or the area under the curve (AUC) were found between patients with moderate renal failure and healthy subjects.

Dilatory effects of phosphodiesterase inhibitors on human hand veins in vivo.

Objective: To compare the venodilator potencies of the phosphodiesterase (PDE) III inhibitors amrinone and enoximone with the unspecific PDE inhibitors theophylline and pentoxifylline in human hand veins in vivo.

Methods: Eighteen healthy nonsmokers (16 men and two women) were studied using the dorsal hand vein technique. After preconstriction with the selective alpha1-adrenergic-receptor agonist phenylephrine dose-response curves were constructed for amrinone (1-270 microg x min(-1)), enoximone (1-270 microg x min(-1)), theophylline (5-1500 microg x min(-1)) and pentoxifylline (2-877 microg x min(-1)) in a random order on separate occasions.

Determination of drugs in biological fluids by high-performance liquid chromatography with on-line sample processing.

An automated two column HPLC system with the new packing material LiChrospher RP-18 ADS (alkyl-diol-silica) was tested for the determination of several drugs and metabolites (talinolol, celiprolol, metoprolol, oxprenolol, triamterene, trimethoprim, tiracizine, articaine, detajmium, ajmaline, lamotrigine) in various biological fluids (serum, urine, intestinal aspirates, supernatants of cell cultures and supernatants after protein denaturation). The method allows the direct injection of biological fluids into a reversed-phase HPLC system and on-line clean-up and sample enrichment by a column-switching technique. Precision, accuracy and sensitivity were similar to conventional assays as described in the literature.

Effect of high dose verapamil on restenosis after peripheral angioplasty.

Objectives: We sought to determine whether treatment with high dose verapamil prevents restenosis in patients at high risk for reoccurrence after successful percutaneous transluminal coronary angioplasty (PTCA).

Background: Restenosis is the major limitation of PTCA. Calcium antagonists have demonstrated some potential as inhibitors of this process.

Epidemiological features of Adamantiades-Behçet's disease in Germany and in Europe.

The German Registry of Adamantiades-Behçet's disease was founded in 1990 in Berlin and it provides current data on the epidemiology, the clinical manifestations and the course of the disease in Germany on a continuous basis. A total of 218 patients, including 89 German and 100 Turkish patients, had been reported to the German Registry until October 1997. One hundred and ninety-six patients fulfilled the criteria of the Behçet's disease classification tree.

Clinical pharmacokinetics of articaine.

Articaine is the most widely used local anaesthetic agent in dentistry in a number of European countries. The amide structure of articaine is similar to that of other local anaesthetics, but it contains an additional ester group which is quickly hydrolysed by esterases. High performance liquid chromatography has been used to determine the concentrations of articaine and its metabolite articainic acid in serum.

Pharmacokinetics of candesartan cilexetil in patients with renal or hepatic impairment.

Five clinical studies were conducted to investigate the pharmacokinetic profile and safety of candesartan cilexetil in patients with either normal or impaired renal or hepatic function. Participants in these open-label, single- or parallel-group prospective studies were administered candesartan cilexetil 8 or 12 mg as a single oral dose and then, in all but one study, as a repeated once-daily oral dose regimen. A total of 94 patients of either gender aged between 18 and 75 years with normal or mild to moderate hepatic dysfunction (Study 1) and normal or mild to moderate/severe renal dysfunction (Studies 2-5) were included.

Influence of Carbimazole on Serum Levels and Haemodynamic Effects of Digoxin.

Although the influence of thyroid dysfunction on the effectiveness and disposition of drugs has been extensively studied, the pharmacokinetic/pharmacodynamic interactions between cardiac glycosides and antithyroid drugs have not been investigated. This possibility arose following the clinical observation of relatively lower digoxin plasma levels in 1 patient concomitantly treated with Carbimazole. We therefore examined the influence of a single oral dose of 60mg Carbimazole or placebo on the steady-state serum levels and haemodynamic effects of digoxin (0.

Different concepts in first-line treatment of essential hypertension. Comparison of a low-dose reserpine-thiazide combination with nitrendipine monotherapy. German Reserpine in Hypertension Study Group.

Low-dose combination therapy has been proposed as a rational first-line approach to hypertension treatment. We compared the efficacy and tolerability of the fixed combination of reserpine (0.1 mg) plus the thiazide clopamid (5 mg) with its single components and the calcium-antagonist nitrendipine (20 mg) in a randomized, double-blind, parallel study of 273 hypertensive patients with diastolic blood pressure (BP) between 100 and 114 mm Hg.

Cytotoxic therapy and pregnancy.

The use of cytotoxic agents during pregnancy may be unavoidable in order to ensure maternal survival-despite the dangers to the developing fetus. We review 217 such cases published between 1983 and 1995, classifying them into 5 groups according to whether the cytotoxic drugs were used to treat leukaemias, malignant lymphomas, severe rheumatic diseases, gynaecological/breast neoplasms, or other grave conditions. Various factors, such as the drug type, dose, and timing to exposure to gestational age, are analysed with respect to the outcome of these pregnancies (teratogenicity, stillbirths, spontaneous abortions, prematurity, etc.

Coronary anomaly in Behçet's syndrome.

A 39-year-old man who was known to have Behçet's syndrome suffered an acute posterior-wall myocardial infarction. The infarction occurred 13 years after the onset of the Behçet's disease, which had been marked by recurrent chorioretinitis and thrombosis of the retinal veins of both eyes. Coronary arteriography showed occlusion of the circumflex branch and an aneurysmal fistula between the left main branch and the pulmonary artery.