Impact of the CYP2D6 genotype on the clinical effects of metoprolol: a prospective longitudinal study.

After administration of metoprolol, plasma concentrations of the drug are markedly higher in CYP2D6 poor metabolizers (PMs) than in non-PMs. In a prospective double-blind 3-month study, we investigated whether this translates into differences in metoprolol's effects after initiation of therapy. Despite administering equal doses to PMs and non-PMs, metoprolol plasma concentrations were 4.

Bioavailability of diclofenac potassium at low doses.

Aim: Diclofenac-K has been recently launched at low oral doses in different countries for over-the-counter use. However, given the considerable first-pass metabolism of diclofenac, the degree of absorption of diclofenac-K at low doses remained to be determined. The aim of this study was to determine the bioavailability of low-dose diclofenac-K.

Effect of amiodarone on the plasma levels of metoprolol.

On average, metoprolol plasma concentration is doubled after an amiodarone loading dose (1.2 g/day over a period of 6 days). However, the individual amount of this drug interaction depends on the CYP2D6 genotype.

Carvedilol but not metoprolol reduces beta-adrenergic responsiveness after complete elimination from plasma in vivo.

Background: Carvedilol but not metoprolol exhibits persistent binding to beta-adrenergic receptors (beta-ARs) even after washout in cell culture experiments. Here, we determined the significance of this phenomenon on human beta-ARs in vitro and in vivo.

Methods And Results: Experiments were conducted on human atrial trabeculae (n=8 to 10 per group).

CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study.

Objective: Treatment with antidepressants is frequently associated with adverse effects or insufficient clinical response. Several antidepressants are metabolized by cytochrome P450 (CYP) 2D6. The activity of this enzyme markedly varies among individuals from poor to ultrarapid metabolism on the basis of the polymorphism of the CYP2D6 gene.

Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects.

Objective: The CYP2D6 genotype is a major determinant of interindividual differences in metoprolol plasma clearance. Cytochrome P450 2D6 (CYP2D6) poor metabolizers exhibit 3- to 10-fold higher plasma concentrations after administration of metoprolol than extensive metabolizers. However, the impact of the CYP2D6 genotype on the occurrence of adverse effects of metoprolol remains controversial.

Effect of the CYP2D6 genotype on metoprolol metabolism persists during long-term treatment.

The beta1 selective beta-blocker metoprolol is metabolized predominantly but not exclusively by CYP2D6. Due to the polymorphism of the CYP2D6 gene, CYP2D6 activity varies markedly between individuals. Consequently, after short-term administration metoprolol plasma concentrations were found to be several fold higher in poor metabolizers than in extensive metabolizers.

Prospective crossover comparison of carvedilol and metoprolol in patients with chronic heart failure.

Objectives: This study investigates the effects of a change of beta-adrenergic blocking agent treatment from metoprolol to carvedilol and vice versa in patients with heart failure (HF).

Background: Beta-blockers improve ventricular function and prolong survival in patients with HF. It has recently been suggested that carvedilol has more pronounced effects on left ventricular ejection fraction (LVEF) compared with metoprolol.

[Stimulation of endogenous TSH secretion and endocrine orbitopathy].

In 81 patients the thyrotoxicosis was controlled with antithyroid drugs only. Ophthalmopathy was seen in 53 patients when therapy was started. Patients with ophthalmopathy stage V or VI were excluded from this study.

[Radiation therapy of endocrine orbitopathy. 1st communication: clinical results (author's transl)].

Ten patients with serious endocrine orbitopathy underwent radiation therapy of the retrobulbar orbital tissue. Between the 2nd and the 13th week preceding radiotherapy, exacerbation of the clinical symptoms had appeared in all the patients, and distinct symptoms of infiltrative tissular processes were seen beside bulbar protrusion. Of the cases, 5 suffered from marked extra-ocular myopathy, 6 from corneal lesions, and one patient had lost his visual faculty.

[The normal liver-spleen scintigram with the gamma camera (author's transl)].

In 104 patients without liver disease, liver spleen scintigrams were analysed according to uniform criteria. The scintigrams were taken after application of 99mTc-sulfur colloid in at least six projections with the gamma camera and coupled data processing. As a significant difference compared to scanner scintigraphy, a non-homogeneous storage pattern is frequently also found in the healthy liver, especially in the ventral projection.

[Effective out-patient treatment of gastric ulcer with proglumide: preliminary results (author's transl)].

In a double-blind trial 16 persons with gastric ulcer and 35 with duodenal ulcer were treated as out-patients with 1200 mg proglumide daily or 1320 mg magnesium tricilicate daily (as an "active placebo") for four weeks. The ulcers were assessed by endoscopy before and after treatment. The gastric ulcers disappeared in 75% of patients receiving proglumide (six of eight subjects) but in only 25% of those on the placebo (two of eight).

[Pathogenesis of Basedow's disease].

Thyroid antibodies and thyroid-stimulating factors (LATS and LATS-Protector) have been controlled 53 patients with Graves' disease during antithyroid drug treatment. It has been demonstrated that dosage is higher and duration of treatment has been more protracted in antibody-positive thyrotoxicosis than in patients without these antibodies. Thyroid antibodis have been found only in patients with detectable thyroid-stimulating factors, which are identified as immunglobulins.

[Embolism by ultrasound-thrombolysis (author's transl)].

By ultrasound it is possible to destroy thrombi intravascular and remove them by a hollow flexible probe at the same time. Experiments were now performed in 6 dogs with 2-9 days old thromboses in the femoral or iliac veins, to detect embolisation during ultrasound-thrombolysis. Parameters were pulmonary angiograms and lung scans.

[Effect of experimentally induced hyperthyroidism on zona glomerulosa from adrenal cortex of the rat (author's transl)].

By histochemical and histometrical methods the the effect of l-triiodothyronine on the zona glomerulosa from rat adrenal cortex was investigated. Glucose-6-phosphatedehydrogenase and 3-beta-OH-steroiddehydrogenase activities were determined in slices of adrenal cortex. No increase in activities of these enzymes was observed after treatment with l-triiodothyronine.

[Clinical significance of serum magnesium concentration in thyrotoxicosis (author's transl)].

Thyrotoxicosis is associated with hypomagnesemia. Therapy leads to restoration of serum magnesium concentration. The clinical significance of the disturbance in magnesium metabolism is discussed on results of two groups of patients with hyperthyroidism.