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J Vollmar

Publications and source records attributed to J Vollmar.

At least 19 recordsLinked to original sources
PubMed1996

Substitution of conventional cyclosporin with a new microemulsion formulation in renal transplant patients: results after 1 year.

BACKGROUND: A new galenic form of cyclosporin A has been developed, based on microemulsion technology. The bioavailability of the compound is relatively independent of food intake and bile flow. It was the purpose of this prospective clinical trial to study the safety of the microemulsion form of cyclosporin A. METHODS: Three hundred and two renal transplant patients, stratified according to transplant age, were switched from the conventional to the new microemulsion formulation of cyclosporin A. A 1:1 conversion ration was used. Measurements included CsA levels, S-creatinine, liver enzymes, uric acid, and blood pressure. Measurements were performed at baseline and on days 4, 8, 15, 29 and months 3, 6 and 12 after conversion. Dose adjustments were performed to achieve through levels of 80-120 ng/ml. RESULTS: Within the 12-month observation period the cyclosporin dose was reduced by 14.7% (from 204 +/- 60 mg/day at baseline to 174 +/- 51 mg/day after conversion, P < 0.001). Acutely, i.e. by day 8, 1:1 dose conversion resulted in a modest increase of mean drug through levels (from 114 ng/ml at baseline to 120 ng/ml, P < 0.01). This increase was accompanied by an increase in serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in uric acid values (P < or = 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decrease (P < 0.05). After 1 month, drug through levels had decreased to baseline (112 ng/ml) and remained there until month 6. They were significantly lower after 12 months (102 +/- 33 ng/ml), P <0.001). Creatinine clearance values increased to above baseline at 6 and 12 months. Within the 1-year period there occurred 24 (= 8%) episodes of biopsy proven rejection and seven episodes of cyclosporin-attributed nephrotoxicity. CONCLUSIONS: The 1:1 conversion from conventional cyclosporin A to the microemulsion formulation s efficacious and safe, but an initial dose reduction of 10% is advised in patients with through levels in the high-normal range.

Administration, Oral↗
PubMed1996

Conversion to microemulsion cyclosporine in stable renal transplant patients: results after one year.

We switched 302 renal transplant patients from the conventional to a new microemulsion formulation of cyclosporine, to study the latter's safety and efficacy. We used a simple 1:1 conversion of the patient's total daily dose. We measured trough drug levels as well as serum creatinine, liver enzymes, uric acid, and blood pressure values at baseline and at days 4, 8, 15, 29, and months 3, 6 and 12 after drug substitution. Dose adjustments directed at trough levels 80-120 ng/ml were performed, starting at day 8. Within the 12-month observation period, the cyclosporine dose was reduced by 14.7% (204 +/- 60 mg/day baseline vs 174 +/- 51 mg/day after conversion, p < or = 0.001). By day 8, the 1:1 dosage conversion resulted in a modest mean increase in drug trough levels (114 ng/ml baseline vs 120 ng/ml, p < or = 0.01). This increase was accompanied by an increase in serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in uric acid values (p < or = 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decreased (p < or = 0.05). After one month, drug trough levels had decreased to baseline (112 ng/ml) and remained there until month 6. They were significantly lower after 12 months (102 +/- 33 ng/ml, p < or = 0.001). Plasma creatinine values decreased to below baseline by month 6 (p < or = 0.001) and month 12 (p < or = 0.001). Twenty-four (8%) biopsy proven rejection episodes and 7 cases of cyclosporine attributed nephrotoxicity occurred in these 302 patients within these 12 months. We conclude, that a 1:1 conversion from conventional to the microemulsion form of cyclosporine is efficacious and safe. However, we advise an initial 10% decrease in dose reduction in those patients whose trough levels are in the high-normal range.

Adult↗
PubMed1995

Clinical experience transferring kidney transplant patients from Sandimmun to Sandimmun Neoral--results after 3 months.

The new galenic formulation of cyclosporine prepared as microemulsion (Sandimmun Neoral, SN) shows a significantly improved correlation between both trough level (Cmin) and dose. Moreover, since the bioavailability is increased by 20 to 30% on average, it may lead to a drug overexposure in so far malabsorbing patients. In order to assess safety and to establish an appropriate procedure to switch patients safely from conventional Sandimmun to SN, we initialized an open, stratified (transplant age) clinical trial enrolling 302 patients of our outpatient clinic. We used a simple 1:1 conversion of the patient's total daily dose. Trough drug levels, as well as serum creatinine, liver enzymes, uric acid, and blood pressure values were measured at baseline, at days 4, 8, 15, 29, and at month 3 after drug substitution. Within the three month observation period, the cyclosporine dose was reduced by 14.2% (204 +/- 60 mg/day baseline vs. 175 +/- 54 mg/day after conversion, p < 0.05). By day 8, the 1:1 dosage conversion resulted in a modest mean increase in drug trough levels (114 ng/ml baseline vs. 120 ng/ml, p < 0.05). This increase was accompanied by a slight increase in mean serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in mean uric acid values (p < 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decreased (p < 0.05). Parallel to dosage reduction, drug trough levels had decreased after 1 month to baseline (112 ng/ml) and remained there for the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Availability↗
PubMed1990

Morphological characterization of carotid artery stenoses by ultrasound duplex scanning.

Ulcerations and intraplaque hemorrhages are thought to play an important role in the development of neurological deficits in carotid artery stenoses. To assess the ability of duplex scanning to predict plaque morphology we compared different sonographic criteria (plaque border, plaque density, plaque structure) with the morphological findings in 169 consecutive carotid endarterectomies (144 cases with diameter reduction greater than 50%). Two percent of the sonograms were inadequate, and 20% showed poor image quality. Regular plaque borders revealed a smooth or at most minimally ulcerated surface in 92%. Grossly ulcerated stenoses, however, were only found in 27% of the irregular plaques. Moreover, the plaque border was nonvisible in 35% of all cases. Simple, fibro-atheromatous plaques were found to be echogenic in 72% and echolucency was present in 80% of the stenoses with relevant intraplaque hemorrhage. In conclusion, duplex scanning proved to be capable of detecting smooth, fibro-atheromatous stenoses with high accuracy. Ulcerations, however, cannot be predicted reliably, and intraplaque hemorrhage cannot be differentiated from atheromatous debris.

Carotid Arteries↗
PubMed1990

Ciamexone in endocrine orbitopathy. A randomized double-blind, placebo-controlled study.

The influence of ciamexone on the activity and course of endocrine orbitopathy was investigated. Fifty-one patients with active orbitopathy classes II-VI were allocated randomly to two groups: over a period of six months, 26 patients received 300 mg/day ciamexone and 25 patients received placebo tablets. In both groups, prednisolone was administered in addition in the first four weeks. Ophthalmological investigations and clinical tests as well as orbit sonography were carried out before as well as one, three and six months after the beginning of therapy. Before and after treatment, computer tomography of the orbit was performed. Symptoms and signs did not show any significant improvement one and six months after therapy. No differences between the two therapy groups were observed. Detailed examination did not reveal any preferential action of the product on individual parameters. Sonography and computer tomography showed no significant alterations of the thickness of the oculomotor muscles. Thus administration of 300 mg ciamexone once a day as compared with placebo did not show any effect on the course and activity of endocrine orbitopathy.

Adjuvants, Immunologic↗
PubMed1990

[Biochemical aspects of the evaluation of fixed drug combinations].

Various disciplines have to contribute to the general problem of the evaluation of fixed dose combination drugs, as for instance (clinical) pharmacology, biometry, scientific drug regulations and public health officials. The EC guideline 75/318/EWG and its eludications as well as the German "Arzneimittelprüfrichtlinien" of Dec. 14, 1989 (as referred to in the "Arzneimittelgesetz" of 1986) required that such issues concerning fixed dosage combination drugs must be considered and taken into account. In this framework it is the responsibility of biometry to both to guarantee the use of a valid study design to assure interpretation of the results and to quantify the reliability of pharmacological and clinical considerations. The following paper is concerned with biometrical aspects of the combination drug problem. Basic considerations from a clinical or a pharmacological point of view with respect to the question of whether fixed combination drugs are reasonable or not are not discussed. To support the use of combinations of drugs, a central argument is the improvement of the benefit risk relation compared with that of an adequate monotherapy. Beyond this the fixed combination drugs require additional arguments regarding the enhencement of the safety or the simplicity of the therapy fixing the ratio. It follows that fixed combination drugs have to be supported twice, first with respect to the combination itself, and second with respect to the fixed mixing ratio of its components. The biometrical aspects of the assessment of the gains from (fixed) drug combinations are related to the kind of benefit/risk improvement that is expected. In the first section we discuss some possible types of benefit and risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Diurnal lipid and lipoprotein profiles in hypertriglyceridemic patients with bezafibrate and clofibrate.

Thirty hypertriglyceridemic patients were treated under metabolic ward conditions for 10 days with either placebo, clofibrate (500 mg t.i.d.) or bezafibrate (200 mg t.i.d.) in a randomized, double-blind study. In addition, patients received an isocaloric prudent diet. On day 10 a diurnal lipid and lipoprotein profile was carried out. Compliance to medication was good. Each treatment led to significant reductions of fasting triglycerides and cholesterol. Lowering of fasting and integrated diurnal triglycerides was greatest with bezafibrate. HDL-cholesterol profiles were highest with this drug. A strong correlation between fasting and diurnal triglycerides was observed. Triglyceride-lowering therapy must therefore aim at fasting triglyceride values as low as possible.

Adult↗
PubMed1986

Investigations on the exogenous influencing of the spontaneous tumour rate in rats.

72 male and 72 female rats of the strain Can-Hoe-Wiga received standard diet in a long-term study (24 months). A group of equal size received the beta-blocker BM 51.052 administered at a dose of 900 ppm in the feed. The animals in the drug group showed a 20 to 30% delay in body weight gain in comparison with the control animals. These drug-treated animals showed, similarly to experiments with a restrictive diet, a lower death rate, fewer glomerulopathies, and lower creatinine and protein levels in the serum. In addition, there were fewer tumour bearers, the total number of tumours was less, and the malignancy and formation of metastases was reduced. This experiment shows the importance which should be attached to the course of body weight gain during a long-term study. Only if these parameters are taken into consideration, an interpretation of the experimental results is possible.

Animals↗
PubMed1985

Effect of bezafibrate during 4.5 years of treatment of hyperlipoproteinaemia.

Bezafibrate in a dosage of 200 mg 3 times daily was given to 24 patients with type II A (n = 8), II B (n = 1) and IV (n = 15) hyperlipoproteinaemia for 4.5 years. In type II A the content of total cholesterol and that of low density lipoprotein in serum decreased by 10-23 and 11-34 percent over the years compared to pretreatment. In type IV the content of total triglycerides and that of very low density lipoprotein decreased by 28-39 and 38-52 percent, respectively, over the years. High density lipoprotein cholesterol increased in both types. The "atherogenic index" was reduced by the drug. The effect remained through the 4.5 years of treatment. Compliance to the drug was good. Changes in safety laboratory parameters were minor and reversible. No subjective side-effects occurred and no cases of gallbladder disease or cancer were noted. It is concluded that bezafibrate is a safe, convenient and effective serum lipid-lowering drug suitable for the use in primary and secondary prevention of atherosclerotic disease.

Bezafibrate↗
PubMed1985

[Abdominal aortic aneurysm. Change in diagnosis and therapy].

The improved diagnostic approach using computerised tomography and ultrasound investigation resulted recently in a remarkable increase of early diagnosed abdominal aortic aneurysm. Simultaneously in the last decennium the number of elective interventions has been increased 4-6 times. As a result of simplification and standardisation of the operative technique (dissection resp. inlay-technique) the operative mortality for elective surgery has decreased to 1-3%. Statistical datas proved a significant increase of life expectancy for operated patients. Interventions for ruptured abdominal aortic aneurysms are still loaded with a high risk (mortality rate 40-75%). Both elective and emergency vascular repairs should be done by well trained vascular surgeons and should not be a challenge for general surgeons to do sporadic vascular surgery.

Aorta, Abdominal↗
PubMed1985

[Aortofemoral bifurcation bypass--effect of the anesthesia procedure (NLA, thoracic continuous catheter peridural anesthesia) on circulation, respiration and metabolism. Intraoperative circulatory reactions].

51 patients who were selected for aorto-bifemoral bypass operation (infrarenal aortic aneurysm, iliac or iliofemoral occlusive disease) were randomized into two groups. 26 patients were operated on under neuroleptanaesthesia and 25 patients had a continuous thoracic epidural, which was supplemented with a light general anaesthesia during the operation. All patients were optimally volume loaded prior to surgery. The most marked haemodynamic alterations (tachycardia, arterial hypertension, increase of cardiac index, left ventricular stroke work index and cardiac minute work) were provoked by eventration of the gut. In the epidural group, these changes were attenuated and in contrast to the neuroleptanaesthesia group, there were a few patients who had a serious fall in blood pressure. These reactions were regularly accompanied by a generalized flush which led to the hypothesis that they were caused by the release of intestinal hormones, reactive peptides and neurotransmitters, from the mechanically irritated gut. Clamping of the aorta was relatively uneventful. Heart rate and cardiac index decreased in both groups but mean arterial pressure and pulmonary capillary wedge pressure remained stable. Systemic vascular resistance increased slightly in the neuroleptanaesthesia, but not in the epidural group. Declamping was followed by significant but transient falls in systemic vascular resistance and arterial pressure in both groups, despite sufficient volume loading before opening the clamp. In the neuroleptanaesthesia group these changes spontaneously returned to normal; in the epidural group 6 patients received vasopressors or positive inotropic drugs. These results indicate the following: Epidural anaesthesia prevents hypertension and tachycardia and lowers cardiac minute work. Eventration of the gut, acute blood losses and declamping of the aorta may be critical situations, which can lead to profound hypotension. Under neuroleptanaesthesia eventration of the gut is followed by tachycardia and hypertension whereas blood losses and declamping are not as critical as when an epidural is used. Only experienced anaesthetists should use epidural anaesthesia for aortic surgery. An intensive monitoring of haemodynamic function during this form of anaesthesia is mandatory.

Adult↗
PubMed1985

Diurnal lipid and lipoprotein profiles with bezafibrate and clofibrate in healthy volunteers.

Diurnal lipid and lipoprotein profiles were measured in 28 healthy volunteers after 10-day treatment periods with placebo, bezafibrate (200 mg 3-times daily) or clofibrate (500 mg 3-times daily) in a double-blind, parallel trial. The two drugs lowered fasting triglyceride and cholesterol levels (p less than or equal to 0.05 for cholesterol with bezafibrate vs placebo). Diurnal triglyceride profiles were lowest with bezafibrate due to lowest fasting triglycerides. Alimentary lipaemia with placebo was mild and due to increased VLDL-triglycerides, while the other lipoprotein lipids and total plasma cholesterol remained virtually unchanged during the day. Bezafibrate (half-life 2 hours) and clofibrate (half-life 15 hours) gave similar diurnal triglyceride patterns. The diurnal values were dependent on the fasting values. Changes in the cholesterol/phospholipid ratio during the day may be related to altered post-prandial composition of HDL.

Adult↗
PubMed1984

The influence of age and multimorbidity on the pharmacokinetics and metabolism of spironolactone.

The pharmacokinetics of the metabolites of spironolactone (canrenone and fluorigenic metabolites) were investigated in 10 geriatric female patients with multimorbidity after a multiple daily oral administration of 100 mg spironolactone under steady state conditions. The concentration determinations were carried out simultaneously with a specific HPLC method and a less specific fluorimetric method. On comparison of the pharmacokinetic parameters with the respective values of a control group of younger healthy female subjects, the serum concentrations in the elderly patients were found to be twice as high. In addition, a statistically significant positive correlation with age was found in the patients for the kinetic parameters investigated. A positive correlation existed between erythrocyte count and the pharmacokinetic parameters of canrenone, especially with the area under the concentration/time curve. No such association was detectable, however, for the total fraction of fluorigenic metabolites (including canrenone). The results of our investigation indicate that, in addition to the known high binding of canrenone to plasma proteins, there is also possibly a (restrictive) binding to erythrocytes.

Aged↗