Search PubMed⌕ Search

Biomedical subjects

N Rietbrock

Publications and source records attributed to N Rietbrock.

At least 55 records · Page 3Linked to original sources
PubMed1991

Pharmacodynamic profile of verapamil in relation to absolute bioavailability: investigations with a conventional and a controlled-release formulation.

The absolute bioavailability F and response (prolongation of the PR interval) of verapamil after single doses of the same oral formulation administered on two different days were investigated in 16 male subjects with an 80 mg fast dissolving and a 240 mg controlled-release preparation and compared with a bolus injection of 5 mg of verapamil. The absolute bioavailability was 23% in both investigations for the 80 mg preparation and 32% in both investigations for the 240 mg dosage form. The individual values obtained for tmax, cmax, F, and AUC0-alpha showed a wide intersubject variability; therefore, no significant differences could be observed between the two trials for each dosage, but significant differences existed between the investigations of the two preparations. After intravenous administration, concentration-effect curves were about twofold left shifted when compared with the 80 mg tablet and about threefold left shifted when compared with the 240 mg tablet. Estimation of the drug input rate showed significantly (p less than 0.05) smaller values when the controlled-release tablet was given (80 mg tablet: 95.1 and 107.7 mg/h; 240 mg tablet; 55.8 and 46.3 mg/h). Thus, the effect and bioavailability of verapamil show sufficient intersubject reproducibility if the same formulation is given. The differences between the responses and the bioavailability after administration of different preparations may be related as well to the drug absorption rate and the stereoselective first pass of verapamil as to saturation of first-pass metabolism.

Administration, Oral↗
PubMed1991

Converting enzyme inhibition in coronary artery disease: a randomized, placebo-controlled trial with benazepril.

The antiischemic efficacy of the converting enzyme inhibitor (CEI) benazepril was investigated in a randomized, placebo-controlled double-blind study with intraindividual crossover in 11 normotensive patients with angiographically proven coronary artery disease. Bicycle ergometry and 24-h ambulatory ECG were performed before and after 2-week treatment with placebo and benazepril, respectively. Plasma concentrations of atrial natriuretic peptide (ANP) and plasma renin activity (PRA) were measured before each exercise test. Maximal exercise-induced ST-segment depression was not significantly influenced by benazepril therapy (placebo 2.09 +/- 1.22 mm, benazepril 1.91 +/- 1.00 mm). Systolic blood pressure/heart rate (SBP/HR) product at maximum workload remained almost constant with 253 +/- 43 with placebo and 253 +/- 39 with benazepril treatment. The number of anginal attacks and ischemic episodes detected by ambulatory ECG were not significantly reduced. PRA increased significantly from 2.18 +/- 3.76 to 9.62 +/- 8.49 ng/ml/h after benazepril (p less than 0.005), whereas plasma concentrations of ANP remained unchanged (28.04 +/- 12.39 vs. 26.73 +/- 11.09 pg/ml). Therefore, measurement of ST-segment depression with exercise in 11 normotensive patients with coronary artery disease produced no evidence of an antiischemic action for the CEI benazepril 10 mg twice daily (b.i.d.) for 2 weeks, but an improvement was observed in six patients.

Adult↗
PubMed1990

Concentrations of isosorbide dinitrate, isosorbide-2-mononitrate and isosorbide-5-mononitrate in human vascular and muscle tissue under steady-state conditions.

The concentrations of isosorbide dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN) and isosorbide-2-mononitrate (IS-2-MN) were determined in plasma (PL), saphenous vein wall (SV) and pectoral muscle (PM) from 8 patients undergoing coronary bypass surgery. The patients were pretreated for 2 days with ISDN 240 mg per day (standard release formulation) in 4 doses of 40 mg and one dose of 80 mg. The plasma and tissue samples were obtained during the operation, 10-12 h after the last dose. Isosorbide-2-mononitrate and isosorbide-5-mononitrate were present in plasma and tissues in the same concentration ranges with molar concentration ratios of 0.88 (IS-2-MN: PM/PL), 0.85 (IS-5-MN: PM/PL), 0.99 (IS-2-MN: SV/PL) and 1.06 (IS-5-MN: SV/PL). Mean ISDN concentrations in tissue were considerably higher than in plasma; the molar concentration ratios were 4.9 (SM/PL) and 7.21 (SV/PL). The accumulation of ISDN in vessel walls may contribute to its greater vascular action compared to the mononitrates, but it may also facilitate the development of tolerance during long-term treatment.

Aged↗
PubMed1990

Dose adjustment of nifedipine in hypertensive patients.

Ten patients with essential hypertension (WHO grade I-II) were treated in an open dose-adjustment study with the standard regimen of slow-release nifedipine 20 mg b.d. for 2 weeks and with an individualized dose for 6 weeks. The optimum dose, defined as that producing a pre-dose diastolic blood pressure (dBP) of 90 mm Hg at steady state, was determined from the individual concentration-effect relationship after a test-dose of 20 mg. On standard therapy, the reduction in pre-dose dBP was inadequate in 4 patients and it was excessive in 1 patient. After 2 weeks of individualized treatment, the required pre-dose antihypertensive effect was obtained in all patients. The individual doses required were 10 mg b.d., 10 mg t.d.s. 20 mg b.d., 20 mg t.d.s. and 20 mg q.d.s. One patient dropped out of the study because of side effects. Loss of the antihypertensive effect was observed in one patient after 6 weeks of treatment. On the optimized dose, the average value of the pre- and 2 h post-dose steady state nifedipine concentrations (27.6 micrograms/l) compared well with model-derived optimum concentrations (28.6 microliters/l) (r = 0.9210). The results show that the dose of nifedipine can be accurately predicted using the individual concentration-effect relationship after a single dose.

Adult↗
PubMed1990

[Non-enzymatic glycation of human serum albumin: influence on thebinding kinetics of the benzodiazepine binding sites].

Human serum albumin was non-enzymatically glycated in vitro and the glycation rate determined using an affinity chromatography method. The influence of glycation on the binding of the model ligand, dansylsarcosine, at the benzodiazepine binding site was determined with a stopped-flow method. Fluorescence time curves were recorded during the binding process. As the glycation rate increased, the association velocity constant, k2, decreased from 533.3 s-1 (glycated albumin 0.048 of total serum albumin) to 218.1 s-1 (glycated albumin 0.158 of total serum albumin). The affinity constant, KA, showed a corresponding decrease from 7.61 x 10(5) l/mol (fraction of glycated albumin 0.048) to 2.60 x 10(5) l/mol (fraction of glycated albumin 0.158). The dissociation velocity constant, however, increased from 17.3 s-1 (fraction of glycated albumin 0.048) to 19.8 s-1 (fraction of glycated albumin 0.158). The inhibition of binding probably occurs via an allosteric mechanism.

Benzodiazepines↗
PubMed1990

Bioaequivalence of sublingual glycerol trinitrate. Bioavailability and haemodynamic effects after application of a fluorochlorohydrocarbons-dependent spray and a new pumping system.

Bioaequivalence of glycerol trinitrate (GTN, CAS 55630) was investigated in 16 healthy volunteers after sublingual application of 2 x 0.41 mg GTN from two different spray-formulations (A: fluorochlorohydrocarbons (FHC)-dependent formulation; B: FHC-free pumping system). Plasma concentrations of GTN (measured by a gas chromatographic method) and haemodynamic effects (measured by digital plethysmography) were monitored 30 min after application. EC50 of the individual concentration-effect curves were calculated and linked to the individual concentration-time curves to establish the time of reaching EC50 (tEC50). AUC0-infinity, Cmax, tmax and the haemodynamic parameters were compared intraindividually (Wilcoxons matched pairs sign rank test), bioequivalence of B to A was tested on the basis of nonparametric 95%-confidence intervals (Tukey). There was no significant difference in the AUC0-infinity (A: 14.2 ng min/ml, B: 16.3 ng min/ml), but significant differences were obtained in Cmax (A: 1.41 ng/ml, B: 2.77 ng/ml, p less than 0.01) and tmax (A: 6.8 min, B: 3.9 min, p less than 0.01). The confidence intervals of the ratio B/A were 0.81-1.56 for AUC0-infinity, 1.3-3.13 for Cmax and 0.50-0.58 for tmax. The GTN-response did not differ after both formulations (EC50 A: 0.441 ng/ml, EC50 B: 0.421 ng/ml), but significant differences were observed for tEC50 (A: 2.82 min, B: 1.05 min, p less than 0.01). Preparation B exhibits a superior bioavailability and a more rapid onset of haemodynamic efficacy.

Administration, Sublingual↗
PubMed1990

[Bioavailability of two slow-release formulations of verapamil].

The bioavailability of 2 slow release formulations (test (P) and reference (R)) of verapamil was investigated in a study with a randomised cross over design, 20 healthy male subjects were included. The mean peak plasma concentration (36.1 +/- 13.1 ng/ml) of the test preparation was reached after 3.75 +/- 0.8 h. The control preparation (R) produced peak values of 34.4 +/- 8.1 ng/ml after 5.6 +/- 3.1 h. MRT (P) was 17.6 +/- 8.2 h and for (R) was 21.1 +/- 7.5 h after (R). The 95-%-confidence interval of the two preparations differed by more than 20%. The release rate of (P) is slower than that of (R).

Adult↗
PubMed1989

[Biological availability of glycerol trinitrate after sublingual administration].

The relative bioavailability of a glyceryl trinitrate (GTN) spray (Nitro-Corangin Spray) compared to that of another GTN Spray was evaluated in 12 healthy male volunteers using an open, randomized cross-over design with two treatment phases. The parameters Cmax, tmax and AUC0-1 showed no statistically significant differences between the two treatments. It is concluded that the two GTN-Sprays may be considered bioequivalent.

Administration, Sublingual↗
PubMed1989

[Bioavailability of sustained-release and nonsustained-release isosorbide-5-mononitrate].

Bioavailability of Sustained Release and Non Sustained Release Isosorbide-5-Mononitrate. In a randomized, open cross-over study in 18 healthy subjects plasma concentration of isosorbide-5-mononitrate (IS-5-MN) after oral administration was determined over 24 h by gas chromatography. A single dose of three sustained release and two standard preparations was given: (A) a capsule (Elantan), 50 mg; (B) a development tablet, 50 mg and (C) a development capsule, 100 mg; furthermore (D) and (E) non sustained release tablets, 40 and 2 x 20 mg, of two different producers. (D) was considered as reference preparation. Standard preparations (D) and (E) were bioequivalent. But maximum plasma concentrations (cmax) of all sustained release preparations were significantly lower from 13% (C) to 53% (A). Also the moment of maximum plasma concentrations (tmax) occurred significantly later between 2 h 40 min and 3 h 50 min. A significant loss in relative bioavailability was observed for (A) with 82.5% and for (C) with 81.4%. (B) achieved the highest relative bioavailability (93.9%) of the sustained release preparations (n.s.). "Therapeutic concentrations" above 100 ng/ml over 24 h were maintained only by (C). Terminal elimination half-lives were calculated between 5.5 and 6.5 h (mean). Plasma concentration-time curves were simulated in steady state.

Biological Availability↗
PubMed1988

[Anti-ischemia effect of enalapril in coronary heart disease. A randomized placebo-controlled double-blind study].

The anti-anginal effect of the ACE inhibitor enalapril, at a dosage of 5 mg twice a day, was tested in a randomised, placebo-controlled double-blind trial on 12 normotensive patients with proven coronary-heart disease. There was a reduction of exercise-induced ST depression by 22% already after the first dose of 5 mg. After 15 days of treatment the ST depression had decreased by 35% (P less than 0.05).

Adult↗
PubMed1988

Drug input rate from the GI-tract. Michaelis-Menten kinetics and the bioavailability of slow release verapamil and nifedipine.

We present evidence, from studies with slow release verapamil and nifedipine, for Michaelis-Menten metabolism during first pass through the liver. Drug input rate from the GI-tract after an oral dose appears to be a determinant of bioavailability. Highest oral bioavailabilities are observed with standard release formulations at high dosage. The bioavailability of slow release formulations with a zero order release kinetic is lower than standard release formulations and related to the dissolution rate in vitro. In addition, (a) the presence of non-linear absorption kinetics offers a further explanation for the considerable inter-patient variability in AUC since the ability of drug to cross the liver is a function of the concentrations attained in portal blood which will be dependent on dissolution conditions prevailing in the GI-tract, (b) depending on the choice of the dose and dosage interval of the conventional release formulation used for comparison and as a consequence of Michaelis-Menten first pass metabolism it is possible to obtain relative bioavailability data showing superiority, equivalence or bioavailability loss with the slow release form. This may explain the discrepancies in bioavailability data for slow release drugs reported in the literature, (c) 'true' estimates of relative bioavailability of a slow release formulation can only be achieved if steady state conditions are present, and the dose and dosage interval of the slow and conventional release formulation are the same, (d) since a slower dissolution rate is 'ipso facto' associated with a lower bioavailability, slow release formulations of verapamil and nifedipine cannot be classified as being 'inferior' or of poorer quality on the basis of bioavailability alone.

Biological Availability↗
PubMed1988

[A model study of bioequivalence of dissolved nifedipine from soft gelatin capsules].

Oral absorption of nifedipine determined from plasma concentrations was studied in 20 healthy subjects aged 19 to 40 years following application of a single soft gelatin capsule as a generic preparation (P) and a reference preparation (R) containing 10 mg nifedipine. Nifedipine was measurable in plasma 15 min after application and maximal concentrations occurred after 0.44 and 0.64 h (mean), respectively. Maximal concentrations Cmax varied between 46.4 and 251.0 ng/ml (median 100.7, mean 112.6) after P and between 35.5 and 279.7 ng.h/ml (median 115.8, mean 125.2) after R. Mean areas under the curves (AUC0-infinity) were 173.6 (median 151.4 P) and 188.6 ng.h/ml (median 163.1, R). The minor differences in the AUC values and Cmax values were not statistically significant. The shorter tmax after the generic preparation (p less than 0.05) is clinically unimportant. Since the bioavailability of P is 97% the two preparations are bioequivalent.

Adult↗
PubMed1987

[Determinants of plasma digoxin and digitoxin concentrations in elderly patients. A multivariate analysis].

In 1063 patients (greater than or equal to 60 years, 531 men, 532 women) the plasma concentration during digitalis maintenance therapy (metildigoxin, n = 356, beta-acetyldigoxin, n = 359, and digitoxin, n = 348) was determined and related to sex, age, body weight, serum potassium, renal function and the prescribed daily maintenance dose. Classification of treatment groups according to renal function (Crea less than or equal to 1.3 mg/dl parallel greater than 1.3 mg/dl) did not show any difference of the mean maintenance doses. In multiple linear regression analyses only a weak relationship between plasma digitalis concentration and the studied variables was found, which could be equally attributed to dose, creatinine and serum potassium in the digoxin derivative groups, whereas for digitoxin only body weight had a significant effect on the plasma concentration. During a maintenance dose of 0.07 or 0.1 mg/die which was given to 87% of patients in the digitoxin group, 70% were found to have plasma levels within the therapeutic range.

Acetyldigoxins↗
PubMed1987

[Bioavailability of delayed-action and non-delayed-action preparations of isosorbide-5-nitrate].

In a randomized crossover study on twelve healthy test subjects, the plasma concentration of isosorbide-5-nitrate (IS-5-N) after oral administration of 40 mg IS-5-N daily from two standard preparations (two tablets Ismo 20 or Corangin 20) and two sustained release preparations with 40 mg or 60 mg IS-5-N (one tablet Corangin 40 or Corangin 60) once a day was determined. The concentrations were measured in the first and in the third dose interval (24 hours). The respective pharmacokinetic parameters (AUC, Cmax and tmax) of the first and the third day only differed slightly. The two standard formulations proved to be bioequivalent. With the two sustained release preparations, maximum plasma concentrations attained after five to six hours were measured which were lower by roughly the factor 2. The sustained release preparations showed a low loss of bioavailability of 13-19% as compared to the nonretarded standard formulations.

Adult↗