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Biomedical subjects

N Rietbrock

Publications and source records attributed to N Rietbrock.

At least 73 records · Page 4Linked to original sources
PubMed1987

Age-dependence and free fatty acid modulation of binding kinetics at the benzodiazepine binding site of serum albumin in neonates and adults determined using fast reaction methods.

Binding kinetics at the benzodiazepine binding site of albumin have been determined as a function of age and fatty acid concentration in serum from 32 neonates (umbilical cord blood), 28 adults aged 23-65 years and 24 adults aged 66-101 years using fluorescence-time curves obtained in a Durrum-Gibson stopped-flow apparatus and the specific marker ligand dansylsarcosine. The binding reaction can be described by a 2-step mechanism characterised by four constants: the association rate constant k2 and dissociation rate constant k-2 for the rate limiting step-2; the affinity constant KA' for the formation of an unstable intermediate complex in step-1; the affinity constant KA for the overall reaction. There were marked differences in k2 between the three groups of subjects with highest values occurring in neonates (mean: 296 s-1), intermediate values in adults aged 23-65 years (mean: 200 s-1, P less than 0.001) and lowest values in adults aged 66-101 years (mean: 144 s-1, P less than 0.001). The dissociation rate constants (k-2) averaged 18.5 s-1 overall, showed only minor changes with increasing age and corresponded to dissociation half-lives of 42 ms, 38 ms and 33 ms for neonates, adults 23-65 years and adults 66-101 years respectively. KA' in neonates and in the group of elderly subjects were lower than in adults aged 23-65 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Bioequivalence of generic drugs and substitution: example of depot verapamil].

Following oral administration of 240 mg Verapamil-HCl as Isoptin RR, Veramex SR 240 and durasoptin SR 240, plasma concentration time curves of Verapamil and ECG changes were determined in 14 healthy subjects. There was a linear correlation between maximal plasma concentration and prolongation of PQ-intervals of the ECG. No hysteresis was observed when the changes in PQ-interval were plotted against plasma concentration. Comparison of concentration and effect profiles showed that the three formulations were not equivalent and a change in therapy from one to the other cannot be recommended.

Blood Pressure↗
PubMed1987

Bioavailability of slow-release co-dergocrine mesylate (dihydroergotoxine) formulations.

The relative bioavailability and plasma concentration profile of dihydroergotoxine as a solution, standard tablets and slow-release formulations have been compared in 12 healthy subjects following the application of 4-5 mg as a single dose or as 2-3 smaller dose units given at 5 h intervals. Plasma dihydroergotoxine concentrations were measured using a sensitive and highly specific radioimmunoassay procedure. The plasma concentration profile after a single 4.5 mg SR-capsule with relative bioavailability 92% (Oral solution, 4.5 mg as single dose = 100%), releasing 80% of the capsule contents within 8 h, was similar to that achieved following the application of 2-3 divided doses at 5 h intervals of a solution (relative bioavailability = 85%), standard tablet (relative bioavailability = 99%) or SR-tablets (relative bioavailability 78%). Slow-release formulations of dihydroergotoxine do not lead to high postdose concentrations as seen with solutions and standard tablets. Application of a single 4.5 mg SR-capsule can maintain prolonged plateau concentrations exceeding 100 pg/ml over 10 h. Reducing the rate of presentation of dihydroergotoxine to the body in the form of slow release formulations or by using spaced doses does not markedly affect bioavailability when compared to a solution.

Adult↗
PubMed1987

[Concentration-time profile of isosorbide dinitrate and its metabolites in plasma following percutaneous resorption of a transdermal therapeutic system].

Percutaneous absorption of isosorbide dinitrate (ISDN), determined from plasma concentrations of ISDN and its metabolites isosorbide 2-mononitrate (IS-2-MN) and isosorbide 5-mononitrate (IS-5-MN), was studied in 8 healthy subjects aged 19 to 25 years following application of a single plaster containing 40 mg ISDN to the hairless skin on the left side of the chest for 72 h. ISDN and mononitrates were measurable in plasma 2 h after application and maximal concentrations for ISDN and mononitrates occurred after 12-16 h and 16 h, respectively. Mean areas under the curves values corrected for the body surface (BS) (AUC0-72 h.BS of 1074, 815 and 3584 nmol.m2.h/l for ISDN, IS-2-MN and IS-5-MN are equivalent to area ratios of 1, 0.8 and 3.3. ISDN metabolism following transdermal application is less extensive than after oral application. The molar nitrate concentration including metabolites, however, is comparatively low reaching approximately 60-80 nmol/l.

Administration, Cutaneous↗
PubMed1987

[Postprandial delay of drug absorption in a gitoformate model].

Oral absorption of gitoformate (Dynocard), a non-renal-dependent cardiac glycoside, was investigated in 8 healthy subjects aged 23-45 years. Plasma concentration-time profiles were obtained once following a 12-h period of fasting, then after intake of a standard high protein meal. The half-life of absorption t1/2a, Cmax and tmax, half-life of elimination t1/2z, and area under the curve (AUC) were compared to evaluate the influence on the bioavailability of gitoformate. t1/2a in the fasting condition (0.36 +/- 0.43 h) is increased when gitoformate is applied after a high protein meal 1.12 +/- 1.12 h). Correspondingly, fasting maximum concentrations are already achieved after 1.4 +/- 1.2 h, but only after 4.8 +/- 1.8 h following the intake of a standard meal. Comparison of AUC (0-168 h) showed that the bioavailability was reduced by 25% after meals.

Absorption↗
PubMed1986

[Dose-dependent serum concentration of ISDN and its metabolites following administration of ISDN-retard. Studies under steady-state conditions].

In a randomized cross-over trial of four groups of patients (total 49 patients) the serum concentrations of isosorbide dinitrate (ISDN), isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5-MN) were measured under steady-state conditions after administration of 20, 40, 60 and 80 mg, respectively, of two ISDN preparations, the two being bioequivalent. At the studied dosage there was a linear relationship between dose and serum concentration of ISDN and its two metabolites in the proportion of 1:6:70. Because the serum concentration of IS-5-MN is so high under steady-state conditions, there is the potential problem of tolerance developing. The drug should therefore be administered at a lower dose twice daily.

Aged↗
PubMed1986

[Pharmacokinetics of glycerol trinitrate].

The absorption, distribution and elimination of glyceryl trinitrate (GTN) in the human are extremely rapid processes. Enzymatic denitration occurs not only in the liver, but also in blood and other organs. The terminal half-life is 2-6 minutes, and clearance about 30 l/min. A large distribution volume indicates that GTN is taken up by peripheral tissues with the consequence that the concentration at the site of action is greater than in blood. The denitrated and glucuronidated metabolites make only a minor contribution to the anti-anginal effect. Within the therapeutic range there is a linear relationship between the applied dose and concentration in blood and this relationship is independent of the mode of application. GTN plasma concentration may fluctuate during prolonged infusions and transdermal application. GTN measurement on multiple plasma samples collected during the dosage interval are therefore required to obtain a reliable estimate of the steady state concentration. Individual dosage regimens are necessary to optimize therapy.

Animals↗
PubMed1985

[Bioavailability of isosorbide dinitrate and isosorbide-5-mononitrate under steady-state conditions].

The relative bioavailability of isosorbide dinitrate (ISDN) and its mononitrate metabolites (IS-2-MN, IS-5-MN) was determined under repetitive dose conditions in 8 healthy volunteers using a randomised, crossover design. Reference drugs were non-sustained release ISDN (Isoket 20) and IS-5-MN (Ismo 20). The relative bioavailability of ISDN after Iso Mack Retard was 69%, for two development products 78% and 79%, and 87% for Isoket Retard. The bioavailability of IS-2-MN and IS-5-MN in sustained release preparations was 6-16% and 1-17% lower, respectively. Whereas the sum total for the area under the concentration-time curve (ISDN and metabolites) for Iso Mack Retard 20 mg was also significantly lower, there was no significant difference in this parameter between Isoket retard 20 and Isoket 20. Taking IS-5-MN non-retard as reference, the bioavailability of IS-5-MN and total nitrate in all ISDN preparations examined was significantly lower.

Adult↗
PubMed1985

[Serum concentration of glyceryl trinitrate (GTN) in transdermal application of GTN dressings of various origins].

Serum levels of glyceryl trinitrate have been determined in eight healthy subjects following transdermal application of four different glyceryl trinitrate plasters using a randomised crossover design. The plasters investigated were Deponit 10, Nitradisc 10, Nitroderm TTS 10 and Nitro-Pflaster-ratiopharm 10. The medians of serum concentrations arranged in decreasing order were 0.17-0.23 ng/ml for Nitroderm TTS 10, 0.13-0.21 ng/ml for Nitradisc 10, 0.08-0.13 ng/ml for Deponit 10, and 0.04-0.09 ng/ml for Nitro-Pflaster-ratiopharm 10. Corresponding areas under the concentration-time curves (AUC 0-24) were 23.15 nmol . h/l (Nitroderm TTS), 20.32 nmol . h/l (Nitradisc), 10.39 nmol . h/l (Deponit), and 5.7 nmol . h/l (Nitro-Pflaster-ratiopharm).

Administration, Topical↗
PubMed1985

[Determination of serum theophylline concentration in ambulatory practice].

Serum-theophylline concentration was measured in 486 ambulatory patients from 407 referring practitioners. They had been on maintenance treatment of 350 mg theophylline (Bronchoretard) twice daily. The concentration was within therapeutic range (8 to 20 mg/l) in 53% of patients, while it was below it in 43% and above in 4%. About half the patients receiving this dose would thus need individual adaptation of dosage, guided by clinical findings and serum concentration, in order to achieve optimal use of the drug's prophylactic and therapeutic potential. It is concluded that (1) theophylline dosage based entirely on standard dose will lead to an unacceptably high percentage of under-dosing; (2) schematic consideration of body-weight, sex, age, living habits, and accompanying diseases proved to be unreliable and insufficient for individual dose determination; (3) dose adaptation to individual clinical situations and serum concentration is necessary in theophylline treatment of ambulatory patients and, in the light of present technical facilities, is cost-effective.

Aged↗
PubMed1985

Absorption kinetics of dihydroergotoxine following oral administration to man.

The absorption characteristics of dihydroergotoxine administered as an oral solution, tablet and retard capsule have been determined in a randomised cross-over investigation in 12 healthy males. The plasma concentrations of dihydroergotoxine produced by the three preparations, measured using a specific and sensitive radioimmuno-assay method over 24 h, exceeded 200 pg ml-1 for approximately 5 h and decayed in a biphasic manner with a slowest measured half-life of 12-14 h. The retard capsule differs from the other two preparations in having a low Cmax (50% of that recorded for the solution) and a clearly defined plateau. The bioavailability of the retard capsule was similar to that for the solution indicating that first-pass metabolism is not significantly increased following a three-fold prolongation in the absorption rate constant. The 20-40% greater bioavailability of dihydroergotoxine solution and retard capsule in comparison with the standard tablet may be due to a reduced contact time with gastric secretions achieved by means of rapid absorption from the stomach (solution) or delayed release at pH 1.5 (retard capsule).

Administration, Oral↗