Search PubMed⌕ Search

Biomedical subjects

N Rietbrock

Publications and source records attributed to N Rietbrock.

At least 109 records · Page 6Linked to original sources
PubMed1982

[Pharmacokinetics and pharmacodynamics of verapamil in healthy volunteers after single oral and sublingual administration].

5-[3,4-Dimethoxyphenethyl)-methylamino]-2-(3,4-dimethoxyphenyl)-2- isopropylvaleronitril (verapamil, Isoptin) was administered p.o. (80 mg) and via the sublingual route (20 mg as the hydrochloride) in 6 healthy volunteers. After p.o. administration the mean peak serum concentration of 125.6 ng/ml was attained on average 80 min later. The half-life for the distribution phase (t1/2a) was 0.95 h and for the elimination phase (t1/2 beta) 6.08 h. After sublingual administration the mean peak serum concentration of verapamil was 26 ng/ml attained on average after 71.7 min. The mean t1/2a was 0.73 h and the mean T1/2 beta 4.39 h. There was an 18.4 min delay after oral administration and 0.8 min delay after sublingual administration before verapamil was detected in the serum. The relative bioavailability of verapamil sublingually was 2.7 (p.o. = 1.0). There were close correlations between the verapamil concentration in serum and the prolongation of the PQ-interval (0.725 sublingually; 0.853 p.o.). Approximately three times higher concentrations of verapamil were required when given by the oral route to produce the same prolongation of the PQ-interval obtained with sublingual administration. The variability of several important pharmacokinetic parameters of verapamil was reduced by sublingual application in comparison to the oral route. The coefficient of variation for the peak concentration, time to peak and t1/2 beta were 49.7%, 25.0% and 26.4%, respectively, after sublingual administration in comparison to 120.6%, 54.7% and 68.9%, respectively, when given p.o.

Administration, Oral↗
PubMed1981

Direct determination of hepatic extraction of verapamil in cardiac patients.

Hepatic extraction of verapamil was determined directly in cardiac patients undergoing diagnostic catheterization and receiving 10 mg verapamil intravenously or intra-arterially. The extraction curves of verapamil concentrations in blood from the ascending aorta and hepatic vein were similar to those reported after single intravenous doses of indocyanine green. The rectilinear fall in concentration lasted 10 to 15 min. Mean hepatic extraction of verapamil in four patients who received intravenous doses was 0.86 (range 0.84 to 0.89) and in four who received intra-arterial doses was 0.87 (range 0.83 to 0.89). These estimates are the same as those for hepatic first-pass extraction determined by indirect methods based on areas under plasma concentration-time curves and requiring calculation of apparent hepatic blood flow. The results were considered to be proof that the first-pass effect of verapamil after oral doses is attributable mainly, if not entirely, to hepatic elimination.

Adult↗
PubMed1981

Verapamil disposition in liver disease and intensive-care patients: kinetics, clearance, and apparent blood flow relationships.

Verapamil kinetics have been determined in liver disease (mainly in cirrhotic patients), in intensive-care patients, and in healthy control subjects. Areas under the concentration-time curves (AUCs) after intravenous 5-mg and oral 80-mg doses were used to calculate systemic blood clearance, intrinsic blood clearance, and bioavailability of verapamil in patients and to calculate apparent hepatic blood flow. Intravenous data showed that verapamil clearance was reduced in all patients with liver disease (mean = -66%), but intensive-care patients were a more heterogenous group in which some patients had increases (five patients; mean = +72%) and others had decreases (two patients; mean = 6-57%) in verapamil clearance. The changes in clearance corresponded to changes in the half-time for the beta-phase (t1/2 beta). Verapamil bioavailability is low, and the intensive-care patients and healthy subjects examined it ranged from 13% to 21%. There was considerable variation in liver disease subjects, in whom verapamil bioavailability ranged from 3.8% to 64%. THe systemic clearance of verapamil correlated linearly with calculated apparent hepatic blood flow (r = 0.99; regression coefficient = 0.87). In the case of one liver patient the kinetic results could be used to confirm the clinical diagnosis of hepatic shunts. It is concluded that there are clinically significant changes in verapamil elimination in liver disease and in intensive-care patients. For patients with normal hepatic vascular anatomy, these changes can be explained in terms of differences in hepatic blood flow.

Adolescent↗
PubMed1981

Digitalis therapy in renal failure with special regard to digitoxin.

When prescribing cardiac glycosides for patients with renal failure, one should consider the different pharmacokinetics of the two most important glycosides, digoxin and digitoxin. Whereas steady state plasma concentrations of digoxin are altered proportionally to renal clearance of creatinine, those of digitoxin remain the same throughout a wide range of renal impairment. The steady state level of both glycosides is partly determined by several clinical factors such as dose, body weight, height, age and serum potassium. However, it is thought that bioavailability, volume of distribution, biotransformation, and total body clearance have the greatest importance for the variability of the plasma glycoside concentrations in patients with normal and with impaired renal function. The bioavailability and biotransformation of digoxin do not vary between healthy subjects and patients with renal insufficiency. As the volume of distribution is smaller in patients with severe renal failure that in normal subjects, the loading dose has to be altered. With decreasing creatinine clearance the total body clearance as well as the renal clearance of digoxin is reduced. On the basis of this assumption maintenance dosage regiments must be adjusted. For digitoxin, the four above-mentioned pharmacokinetic parameters are not altered in patients with renal failure compared to healthy subjects. Moreover, investigations dealing with this problem have suggested an altered protein binding of digitoxin and its metabolites as a possible factor in avoiding accumulation of the drug. However, it is one of the aims of this article to show that a decreased urinary excretion of digitoxin and metabolites is compensated by an increased excretion via the feces. Loading dose and maintenance dose of digitoxin do not have to be adjusted in patients with renal failure.

Biological Availability↗
PubMed1981

Bioavailability of theophylline from a sustained-release aminophylline formulation (Euphyllin retard tablets)--plasma levels after single and multiple oral doses.

The absolute bioavailability of theophylline in two commercially available preparations of aminophylline, a sustained-release formulation (Euphyllin retard tablets) and a solution (Euphyllin solution), was determined in eight healthy volunteers following oral administration of a single dose. Percent bioavailability was obtained by comparing AUC data for theophylline concentration-time curves measured over 24 h with corresponding data following intravenous doses of theophylline. Absorption of theophylline from solution was rapid and complete. Bioavailability amounted to 111 +/- 16% (X +/- SD) compared to i. v. administration. Absorption from the sustained-release tablet appeared more erratic and less complete: the time of peak theophylline concentration varied between 2 and 14 h. The mean plasma level curve showed a plateau between 2 and 14 h bioavailability was 72 +/- 13%. In addition, the sustained-release formulation was administered twice daily (350 mg) for 4 days. Plasma concentrations during multiple dosing of the sustained release formulation were with one exception below 10 mg/l. On day 4 at steady state, peak theophylline concentrations were 8.1 +/- 0.63 mg/l, trough levels 6.2 +/- 1.4 mg/l in the morning and 5.6 +/- 0.67 mg/l in the evening.

Administration, Oral↗
PubMed1980

[Disorders of the ability to distinguish colors during digitalis therapy (author's transl)].

31 hospitalized patients treated with beta-methyl digoxin and 34 treated with beta-acetyl digoxin were examined for color vision disturbances and compared with a control group (n = 17). The serum digoxin concentration was determined radioimmunologically. A significant correlation (p less than 0,01) was found between the severeness of the disturbances in color vision and the concentration of digoxin in the serum. The disturbances concerned different wave length regions. The lapse of time for disturbances in the distinguishing colors is being described in a case of suicidal intoxication.

Acetyldigoxins↗
PubMed1980

Stopped-flow studies on drug-protein binding. 1. Kinetics of warfarin binding to human serum albumin.

We have studied the binding of warfarin to human serum albumin (HSA) with the stopped-flow method. At 37 degrees C the rate constant for the velocity of dissociation of the stable warfarin-HSA complex is 10 S-1 (t50% = 0.07 s). Concentration and temperature dependent association constants for warfarin binding to HSA have been measured (2.5 x 10(5) M-1 S-1 at 6 degrees C, 9.8 x 10(5) M-1 S-1 at 22 degrees C and 15.3 x 10(5) M-1 S-1 at 37 degrees C). Our experimentally obtained relaxation constants are best explained by the existence of 5 equivalent low affinity binding sites for warfarin on the HSA molecule, each capable of conversion into a high affinity site. The measured energy of activation for this conversion is 57.5 kJ M-1.

Humans↗
PubMed1979

[Digoxin concentrations in plasma and tissue. A postmortal investigation (author's transl)].

Postmortal tissue digoxin concentration and prefinal and postmortal plasma digoxin concentrations from 9 patients were determined using the 125J-digoxin radioimmunoassay. The concentration of digoxin in the myocardium of the left ventricle was 61.44 +/- 45.17 ng/g. In the right ventricle the concentration was 36.78 +/- 33.11 ng/g. Higher digoxin concentrations were found in the right atrium (34.93 +/- 21.86 ng/g) than in the left atrium (25.43 +/- 14.57 ng/g). In plasma samples taken after death approximately 62% higher digoxin concentrations were found than in samples of patients in prefinal state. Histological examination revealed positive correlation between in the high varying digoxin concentrations and the pathological conditions of the tissue structure.

Aged↗
PubMed1979

Relationship between dose and plasma level of digoxin and patient characteristics.

The correlation between the daily dose of digoxin, its plasma level and clinical characteristics of 213 patients receiving beta-acetyldigoxin treatment has been evaluated. After logarithmic transformation of lognormally distributed variables multiple linear regression analysis was performed. Eight predictor variables were chosen: sex, age, height, weight, glycoside dose, creatinine and potassium level in serum and dose of spironolactone. The resulting correlation coefficient was 0.46, i.e. only 100 x r2 = 21.4% of the variance of the steady state digoxin plasma level could be interpreted with the aid of these variables. For only 4 of the 8 variables (age, glycoside dose, serum level of creatinine, and spironolactone dose) were partial coefficients of regression and of correlation significantly different from zero. Almost 80% of the variance could not be accounted for. This finding is in accordance with conclusions in the literature.

Adult↗