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Biomedical subjects

W Wurst

Publications and source records attributed to W Wurst.

At least 91 records · Page 5Linked to original sources
PubMed1992

Differential effects of two dihydropyridine calcium antagonists in humans.

We studied the effects after single doses of niguldipine (0.3, 0.6, and 0.9 mg intravenously; 8 and 16 mg orally) and nifedipine (2 mg intravenously; 20 mg orally) in healthy male volunteers in randomized placebo-controlled experiments. Total peripheral resistance (TPR), heart rate-corrected electromechanical systole (QS2c), and preejection period (PEPc) were assessed noninvasively. Both drugs induced a similar pronounced decreased in TRP, indicating peripheral vasodilation, followed by increasing heart rate and cardiac output, a decrease in diastolic blood pressure, and a shortening of the PEPc. QS2c was unchanged after niguldipine. The prolongation of QS2c after oral nifedipine is suggestive of a negative inotropic effect. We conclude that the vasodilatory effects of dihydropyridines may (as for nifedipine) or may not (as for niguldipine) be associated with changes that are suggestive of negative inotropic effects, and that this difference is detectable by noninvasive methods in healthy subjects.

Administration, Oral↗
PubMed1991

Genetic analysis of susceptibility to diabetes mellitus in F2-hybrids between diabetes-prone BB and various MHC-recombinant congenic rat strains.

The occurrence of diabetes mellitus was analysed in F2 hybrids bred from diabetic BB male rats and females of congenic rat strains carrying different major histocompatibility (RT1) haplotypes on the common LEW strain genetic background. Permissiveness for the disease in BB rats is probably determined by class II genes of the RT1 complex, which are also present in normal rats. Class I and class III genes, notably the Hsp70 genes in the class III region, do not appear to be involved. Among the diabetic F2 hybrids, about 90% are shown by DNA analysis to be homozygous for the class II genes of the permissive RT1 haplotype. The segregation patterns are in accord with the action of two independent recessive genes, one of them being RT1-linked.

Animals↗
PubMed1991

Lack of influence of pantoprazole on the disposition kinetics of theophylline in man.

The potential influence of pantoprazole (BY1023/SK&F96022), a newly developed selective inhibitor of the gastric H+,K(+)-ATPase, on therapeutic serum theophylline concentrations was investigated in a crossover study in 8 healthy male volunteers (age 25-30 [median 27] years, body weight 63-80 [median 68] kg). Steady-state serum theophylline concentrations were obtained by a two-step intravenous infusion scheme of approximately 350 mg theophylline each over 0.5 h and subsequently over approximately 10 h, respectively. In the test period, 30 mg pantoprazole were injected over 2 min on 5 consecutive days and theophylline was infused on day 4. In the reference period, placebo was administered i.v. on 2 consecutive days and theophylline on day 1. Serum pantoprazole concentrations were measured up to 12 h, serum theophylline concentrations up to 36 h. Pantoprazole was well tolerated with and without theophylline. There were no clinically relevant changes in blood pressure, heart rate, ECG and routine clinical laboratory parameters. Primary characteristic for confirmative assessment of no interaction was the area under the concentration/time curve (AUC). Lack of interaction in the sense of equivalence was concluded both for theophylline (with and without pantoprazole) and pantoprazole (with and without theophylline), as the 90%-confidence intervals of the AUC-ratio test/reference were within the equivalence range of 0.8 to 1.25. Further explorative analysis of theophylline disposition kinetics revealed this inclusion also for clearance and volume of distribution, but not for the half-life. In the case of pantoprazole, the corresponding 90%-confidence intervals for any of the secondary characteristics clearance, volume of distribution and half-life were within the above mentioned range.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

[Long-term antihypertensive therapy with urapidil. A 3-year open, multicenter trial of tolerance, safety and effectiveness].

Within the framework of an open, multicenter study of 16 physicians treated 206 hypertensive patients with a daily dose of 2 x 30 mg to 2 x 90 mg of urapidil over a period of 3 years. Data are available on 182 patients for the entire study period. 24 patients discontinued the study due to adverse effects (n = 2), an inadequate effect (n = 2), or for reasons unrelated to therapy (n = 20); 58 (28.2%) patients had complaints. The most frequently reported symptoms were nausea, dizziness, drowsiness and fatigue. No relevant changes in laboratory values were observed. Average body weight remained constant and there were no signs of sodium or water retention. In the first year systolic blood pressure was reduced by 25 mm Hg from 174 +/- 13 mm Hg to 149 +/- 10 mm Hg (mean value +/- SD), and diastolic pressure by 17 mm Hg from 103 +/- 6 mm Hg to 86 +/- 6 mm Hg. At the same average dose this drop in BP persisted in the second year (150 +/- 12/86 +/- 7 mm Hg) and the third year (146 +/- 10/85 +/- 7 mm Hg), indicating that there was no decrease in urapidil effect. The pulse rate fell from 77 +/- 8 beats/minute to 74 +/- 6 beats/minute and remained virtually constant over the next 2 years.

Adult↗
PubMed1990

Single intravenous administration of the H+, K(+)-ATPase inhibitor BY 1023/SK&F 96022--inhibition of pentagastrin-stimulated gastric acid secretion and pharmacokinetics in man.

The effects of H+, K(+)-ATPase inhibitor BY 1023/SK&F 96022 on pentagastrin-stimulated acid secretion have been studied in healthy male volunteers (n = 12). The gastric acid response to submaximal pentagastrin-stimulation (0.6 micrograms/h/kg b.w.) was dose-dependently inhibited. A single dose of 5 mg decreased acid output by 22% while after 60 mg and 80 mg secretion was almost completely abolished. A good dose linearity was observed for AUC (0, infinity) and Cmax over the dose range from 5 to 80 mg. Elimination half-life, total clearance and volume of distribution of the parent compound were independent of the dose. The drug was well tolerated up to the highest dose of 80 mg. No clinically relevant influence was found on either laboratory screen or cardiovascular parameters.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

Effect of repeated oral administration of BY 1023/SK&F 96022--a new substituted benzimidazole derivative--on pentagastrin-stimulated gastric acid secretion and pharmacokinetics in man.

Pentagastrin stimulated gastric secretion was measured in 12 healthy male subjects after repeated once daily oral administration of 20 and 40 mg BY 1023/SK&F 96022--a new substituted benzimidazole derivative. Twenty milligrams inhibited acid output compared with placebo by 24% (2.5-3.5 h) and 26% (24.5-25.5 h) after the first oral intake. Inhibition increased to 56% and 50%, respectively, after the seventh oral dose. Forty milligrams inhibited acid output by a mean of 51% (2.5 to 3.5 h) and 52% (24.5-25.5) after the first oral intake. After the seventh dose mean inhibition rose to 85% and 66%, respectively. The drug was well tolerated, no drug-related changes in clinical laboratory, ECG, heart rate and blood pressure were observed. Fasting gastrin serum concentrations tended to increase with both doses, the mean values being within the normal range. AUC, Cmax and t1/2 of the drug after repeated oral intake were not significantly different when compared with a single dose at either 20 mg or 40 mg.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

Pentagastrin-stimulated gastric acid secretion and pharmacokinetics following single and repeated intravenous administration of the gastric H+, K(+)-ATPase-inhibitor pantoprazole (BY1023/SK&F96022) in healthy volunteers.

The objective of the study was to investigate the pharmacodynamics and pharmacokinetics of the gastric H+, K(+)-ATPase inhibitor pantoprazole in man following repeated i.v. dosing. 8 healthy male volunteers aged from 25 to 31 years (median: 29 years), body weight between 72 and 95 kg (median: 82 kg) entered this single-blind two-period cross-over study. Each subject underwent two treatment periods of 5 days each with daily infusion of 15 mg or 30 mg pantoprazole, respectively. A placebo day preceeded the trial. On the placebo day as well as on days 1, 4 and 5 of each treatment period, gastric secretion was stimulated submaximally by a pentagastrin infusion of 0.6 micrograms/h/kg over a period of 4 h, starting one hour before administration of drug or placebo. Repeated once-daily infusion (15 min) of pantoprazole resulted in a rapidly increasing pharmacodynamic effect: as compared to placebo the mean percent inhibition of acid output measured from 1 to 3 h after start of infusion was 22%, 63% and 78% for the 15 mg dose, and 56%, 97% and 99% for the 30 mg dose on days 1, 4 and 5, respectively. The pH also increased in relation to the dose and the duration of treatment. Mean fasting gastrin serum concentrations increased by about 50%, yet remained within the normal range. Only in one subject, one of the individual values was above the upper limit of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1989

Overview of clinical trials with urapidil.

Urapidil has been approved as sustained-release capsules containing 30, 60 and 90 mg, respectively, and as ampules containing 25 and 50 mg for treatment of all grades of hypertension, in several countries in Europe, South America, as well as in Japan and other Asian regions. In general, the treatment should start with 60 mg twice daily, 1 capsule in the morning and 1 in the evening. This schedule may be adapted according to the therapeutic needs. During the last few years, urapidil has been investigated extensively in comparison with several types of established antihypertensive drugs. Urapidil given orally has been tested in comparative trials against placebo, acebutolol, metoprolol, captopril, nifedipine and nitrendipine with responder rates of 40 to 70%. These responder rates are to be expected for a variety of antihypertensive drugs in monotherapy. Further studies with clonidine, prazosin and alpha-methyldopa showed similar responder rates as established for the other antihypertensive drugs studied. Adverse reactions include dizziness, headache and nausea and occasionally tiredness, orthostatic dysregulation and gastric disorders. These symptoms were transient, mostly occurring during the early phases of therapy and disappearing as treatment continued. Adverse effects are considered to be mainly due to blood pressure reduction. Intravenous comparative trials have been performed with urapidil against placebo, diazoxide and sodium nitroprusside. Adverse effects of parenterally applied urapidil are similar to those observed during oral treatment. Specific contraindications for urapidil are unknown. However, as for other vasodilating drugs, intravenous urapidil should not be administered to patients with stenosis of the aortic isthmus or with aortic valve insufficiency.

Administration, Oral↗
PubMed1989

Effect of urapidil on steady-state serum digoxin concentration in healthy subjects.

In an open, randomized, two-period change-over study the effect of urapidil, an antihypertensive agent, on steady-state serum digoxin levels was investigated in 12 healthy male volunteers. The subjects were given digoxin 0.25 mg once daily for 4 days to produce a steady-state digoxin level in serum. At the end of that time the subjects received either digoxin monotherapy or digoxin and concomitant treatment with urapidil 60 mg b.d. for a further 4 days. Subsequently the treatments were changed over. The absorption characteristics Cmax and tmax of digoxin were not altered by concomitant urapidil treatment. The geometric mean and nonparametric 95% confidence limits of digoxin relative bioavailability were 97% (93%-103%). Therefore, concomitant administration of urapidil with digoxin treatments did not appear to alter the rate and extent of absorption of the glycoside.

Adult↗
PubMed1989

A mutant rat major histocompatibility haplotype showing a large deletion of class I sequences.

The LEW. 1LM1 inbred rat strain, which has been derived from a (LEW x LEW.1W) F2 hybrid, carries a major histocompatibility (RT1) haplotype which is distinct from that of the LEW strain (RT1(1)) in that certain RT1.C region-determined class I antigens are not expressed. Here we show that this phenotypic defect is due to genomic deletion of about 100 kb of the RT1.C region. Certain deleted DNA fragments have been cloned from the wild-type DNA into the EMBL4 vector. Five clones have been characterized and are shown to possess different restriction maps and to each carry a single stretch of class I cross-hybridizing sequences. Probes derived from the non-class I coding part of two clones detect fragments which are present in the wild-type but absent from the lm1 mutant. The type of deletion described here in the rat is discussed in the context of H-2D/Q deletions in the mouse.

Animals↗