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Biomedical subjects

H Kroemer

Publications and source records attributed to H Kroemer.

31 records · Page 2Linked to original sources
PubMed1991

Metabolism of verapamil in a family pedigree with deficient N-oxidation of trimethylamine.

The oxidative N-dealkylation of verapamil has been studied in a family of five members with two propositi with an inherited deficiency of trimethylamine N-oxidation (fish-odour syndrome). The results were assessed for possible co-segregation of the trimethylamine N-oxidation phenotype and any observed deficiency in oxidative N-dealkylation. The general pattern of metabolism of verapamil in the five subjects studied was similar to that reported in earlier investigations. Moreover, there were no differences between the two affected subjects and other family members with respect to the metabolic pattern. It is concluded that there is no functional segregation with respect to the mechanisms controlling trimethylamine N-oxidation and verapamil N-dealkylation.

Adult↗
PubMed1988

Reference ranges of viscoelasticity of human blood.

From 204 presumably healthy volunteers 113 (56 women, 57 men) were accepted as reference population for viscoelastic parameters of blood by medical history, physical examination and more than 20 laboratory controls. To avoid bias through processing or calculating, the reference ranges of human whole blood viscoelasticity were given at their native packed cell volumes (see figure 2). The ranges of normal plasma viscosity were determined as 1.16 to 1.41 mPas with the median of 1.31 mPas. The rheological parameters tested are independent of age and gender.

Adolescent↗
PubMed1987

Haemodilution therapy in ischaemic stroke: plasma concentrations and plasma viscosity during long-term infusion of dextran 40 or hydroxyethyl starch 200/0.5.

In 21 patients with ischaemic strokes we have monitored plasma viscosity, total plasma concentration, numeric average molecular weight (Mn), and weight average molecular weight (Mw) of Dextran 40 (dextran) and hydroxyethylstarch 200/0.5 (HES) during 10 days of treatment (days 1-4, 2 X 500 ml; days 5-10, 1 X 500 ml). Plasma concentrations of dextran increased during the first 4 days (8.3 mg X ml-1 on the first day to 18.0 mg X ml-1 on the fifth day), reached an apparent steady state of 17.2 mg X ml-1 during the next 6 days, and declined subsequently with a half-time (t1/2) of 4.03 days. After ten days treatment Mn and Mw were shifted towards higher values. Plasma viscosity increased from 1.26 mPas to 1.69 mPas on Day 10 (p less than 0.01) and was linearly correlated with the total plasma concentration of dextran (p less than 0.001; r = 0.88). Total plasma concentrations of HES averaged 11.7 mg X ml-1 on Day 1 and 12.4 mg X ml-1 on Day 5. The molecular weight distribution did not change during the infusions but decreased in comparison with the administered solution. Plasma viscosity fell from 1.40 mPas to 1.30 mPas at Day 10 (p less than 0.05) and was not related to the concentration of HES. The haemodiluting effect, as indicated by a decrease of the haematocrit, was 22% and 16.8% for dextran and HES respectively. These data suggest several advantages of HES compared with dextran in haemodilution therapy of ischaemic stroke.

Aged↗
PubMed1987

Clinical pharmacokinetic considerations in the use of plasma expanders.

This review deals with the pharmacokinetics of dextrans and hydroxyethylstarch, the most commonly used plasma expanders. The complex composition of these colloidal agents (broad range of molecular weight distribution in vitro and in vivo) confounds their specific assay and meaningful pharmacokinetic analysis. In addition, the time-dependent decline of plasma concentrations of the plasma expanders is at least biphasic, and in some clinical studies the time period for plasma concentration monitoring has been inadequate to characterise the terminal elimination phase. According to their average molecular weight, dextrans can be differentiated into dextran 1, dextran 40, dextran 60 and dextran 70. Metabolism of dextrans by dextranases and extrarenal excretion account for only 2 to 10% of the overall drug loss from the body. Persistence of dextrans in the systemic circulation and elimination by the renal route are dependent on the size of dextrans and their molecular weight distribution. Dextran species with a molecular weight below 15,000 daltons are filtered unrestricted, and consequently the elimination half-life of dextran 1 is relatively short (2 hours) and that of dextran 40 (10 hours) or dextran 60 (42 hours) much longer. In patients with renal insufficiency elimination is impaired in parallel to the reduction in glomerular filtration rate, and smaller doses are advisable in these patients. Dosage reduction might be also indicated if multiple infusions of dextrans are used, since dextran 40 accumulates considerably during long term use (particularly the fractions with higher molecular weights). As only about 50 to 70% of a single dose could be recovered within 48 hours in the urine, the remainder of the dose is probably stored somewhere in the body. Disposition of hydroxyethylstarch is dependent on 2 major factors. As with dextrans, the molecular weight distribution affects the rate of renal elimination. In addition, the degree of substitution with hydroxyethyl groups mainly determines the metabolism of hydroxyethylstarch by alpha-amylase, and thus the overall elimination rate. A higher molecular weight range (e.g. hydroxyethylstarch 450,000 vs 200,000) and a more extensive degree of substitution (e.g. 0.7 vs 0.5) result in a slower elimination, as can be seen by comparing the half-life values of hydroxyethylstarch 450/0.7 (48 days) and hydroxyethylstarch 200/0.5 (20 days). Since only 40 to 65% of an infused dose could be recovered in the urine in humans, the remainder of the dose may be stored in the body. Animal experiments suggest that certain fractions of hydroxyethylstarch might be stored in some tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Dextrans↗
PubMed1987

Pharmacokinetics of famotidine in man.

Famotidine (F) is an effective new H2-receptor antagonist. Knowledge of its pharmacokinetic properties and metabolism is scanty. Therefore, we investigated the disposition of F in 6 healthy male volunteers following a single oral (40 mg) and intravenous (20 mg) dose. F and a metabolite were monitored in plasma or urine by a HPLC method. After intravenous administration plasma levels declined biexponentially with an initial half-life (t1/2) of 0.5 h and a terminal t1/2 of 4.0 h. F was slightly bound to plasma proteins (less than 1 to 15%) and its distribution volume averaged 1.13 l/kg. About 72% of the dose could be recovered as unchanged F in urine. Thus, hepatic clearance contributes to the total plasma Cl of 309 ml/min only 88 ml/min. Consequently, a high hepatic first-pass effect can be excluded. Following oral administration maximum plasma concentrations of 104 +/- 39 ng/ml (mean +/- SD) were observed after 2.3 +/- 1 h. F was eliminated with a t1/2 of 3.6 +/- 1.1 h and its absolute bioavailability ranged from 20 to 66%. In urine an oxidized metabolite could be identified which accounts to about 2% of the given dose. In conclusion, F is rapidly eliminated mainly by the renal route and its t1/2 is slightly longer than those of other available H2-receptor antagonists.

Administration, Oral↗
PubMed1986

[Dextran 40 or HES 200/0.5? Hemorheology of the long-term treatment of ischemic cerebral attacks].

Haemorheological parameters on long-term treatment of ischaemic stroke were measured in two groups of 12 patients receiving dextran 40 or hydroxyethyl starch (HES 200). Both substances similarly lowered haematocrit and whole-blood viscosity. Dextran produced a clear-cut increase in plasma viscosity and red-cell aggregation. The effects were due to a marked increase in the plasma concentration of dextran caused by an accumulation of large molecules. HES 200 improved plasma viscosity and red-cell aggregation. Since these haemorheological parameters are of special importance for improving a disordered microcirculation as would occur at the margins of the ischaemic lesion, HES 200 would seem to be the appropriate plasma expander in long-term treatment with haemodilution. The differences between dextran 40 and HES 200 become the more marked the higher the volume infused.

Blood Viscosity↗
PubMed1978

[Primary shape change of platelets in vitro (author's transl)].

Studies with interference contrast microscopy reveal that platelets undergo a typical shape change within 30--60' after venepuncture, i.e. swelling, formation of large tentacles, tiny protrusions and vesicles at the platelet surface. This "shape change" can be observed in citrated blood and PRP, heparinized blood and EDTA-blood as well. It is enhanced by low incubation temperatures (4 degrees C, 10 degrees C) and delayed at 37 degrees C as compared with room temperature. An increased number of primarily shape changed platelets is found if platelets are strongly mechanically irritated at blood sampling. The shape change is partly reversible in vitro, it is completely or almost completely reversible in vivo. Some antiaggregating agents inhibit the in vitro shape change at varying degrees (Bencyclan, SH 869 greater than ASA greater than D-Propranolol). The shape change is partly inhibited after oral or i.v. administration of ASA. A typical transformation of platelets into "spheric" forms can be observed following the addition of Bencyclan, SH 869 and D-Propranolol to PRP in vitro. The spontaneous "primary shape change" which occurs in PRP or blood after blood sampling is probably different from the secondary ADP-induced shape change. The primary shape change may influence the results of different platelet function and aggregating tests. The shape change kinetics of "healthy" subjects and patients with Hodgkin's disease differ significantly. The described method may gain more clinical interest in the future.

Aspirin↗