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Biomedical subjects

W Kirch

Publications and source records attributed to W Kirch.

At least 199 records · Page 11Linked to original sources
PubMed1989

Cisapride-cimetidine interaction: enhanced cisapride bioavailability and accelerated cimetidine absorption.

The pharmacokinetic interaction between the gastrointestinal motility-stimulating substance cisapride and the H2-antagonist cimetidine was examined in 8 healthy volunteers (25 +/- 2 years of age). Steady-state kinetics of both substances were investigated after separate 1-week treatments of oral cisapride, 10 mg t.i.d., cimetidine, 400 mg t.i.d., and the two drugs combined. Cimetidine increased the cisapride peak plasma concentration from 58 +/- 25 ng/ml to 84 +/- 19 ng/ml (p = 0.01) and AUC0-24 from 509 +/- 289 ng/ml.h to 738 +/- 148 ng/ml.h (p = 0.02). Cisapride shortened the time to the peak concentration of cimetidine from 1.3 +/- 0.6 h to 0.6 +/- 0.2 h (p = 0.005) and reduced the cimetidine AUC0-24 from 11.0 +/- 2.3 micrograms/ml.h to 9.0 +/- 2.0 micrograms/ml.h (p = 0.05). It is concluded that cimetidine inhibits cisapride metabolism, whereas cisapride enhances the gastrointestinal absorption of cimetidine.

Adult↗
PubMed1989

Improved orthostatic dysregulation record after administration of a sustained-release form of urapidil.

The efficacy and safety of urapidil has been demonstrated in a long-term treatment. However, a relatively good record of side effects has been marred by reports of orthostatic dysregulation. This study was designed to examine the blood pressure lowering effect, tolerability and pharmacokinetics of a sustained-release formulation of urapidil. Twelve patients received either 60 mg of sustained-release urapidil (Ebrantil 60) or 50 mg urapidil for experimental reference as a fast-release tablet in single or multiple doses in a randomized, double-blind fashion. To ensure the double blind-character of the study, the tablets were encapsulated. Blood samples for the determination of urapidil (HPLC) were drawn before and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h post application. Blood pressure was measured at 0.5, 1.5, 3, 8, 10 and 12 h post application. An orthostatic test was performed before and at 1, 2, 4 and 6 h post application. Twelve h after the first application, patients received a second capsule or encapsulated tablet and continued medication for two days. On day four, the same procedure as on day one was repeated, except that patients received no evening medication and blood samples and blood pressure were measured at 24, 28 and 32 h post application on the fifth day. The Cmax of sustained-release urapidil was 44% lower than for the single tablet dose and 37% lower after multiple dosing. The peak-trough fluctuation of the steady-state serum concentrations was 29% lower for the sustained-release capsule (138 +/- 45%) compared to the tablet (195 +/- 83%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Negative inotropic action of famotidine].

In a randomized placebo-controlled study, 12 healthy volunteers were treated for one week each with nifedipine 10 mg four times daily or the same dose of nifedipine concurrently with famotidine 40 mg once daily per os. Famotidine did not significantly alter pharmacokinetic parameters of nifedipine. Determination of systolic time intervals showed that pre-ejection period (PEPc) and the ratio of pre-ejection period over left ventricular ejection time (PEP/LVET) were significantly reduced by administration of nifedipine plus placebo. Coadministration of famotidine and nifedipine, however, led to a significant increase in these parameters. Also, administration of famotidine alone to the same subjects led to a significant rise in PEPc and PEP/LVET. In impedance cardiography, stroke volume and cardiac output were significantly reduced by famotidine, whereas the H2-antagonist did not alter heart rate. This observation indicates for the first time that famotidine may exert negative effects on cardiac performance. In our opinion this could be of clinical relevance in elderly subjects or in patients with heart failure.

Adult↗
PubMed1988

Immunological and functional determination of the protease inhibitors, protein C and antithrombin III, in liver cirrhosis and in neoplasia.

Using a new rapid coagulant method, protein C activity (PC act) was determined in liver cirrhosis and malignancies and compared with PC antigen and AT III values. PC was decreased in a more pronounced manner than AT III in liver cirrhosis, mainly due to impaired synthesis. This is of special clinical interest because PC proved to be a high sensible indicator of liver cell dysfunction. Decreased levels of PC act (PC ratio act/ag less than 1) in decompensated liver cirrhosis may be caused by the synthesis of dysfunctional PC and/or vitamin K deficiency with production of undercarboxylated PC most sensitively registered by this coagulant assay. An increased clearance of in vivo activated PC induced by DIC may play an insignificant role. In patients with liver metastases, PC act (but not AT III and immunological parameters) was significantly reduced, supporting the conclusion that in these patients liver dysfunction concomitant with synthesis of dysfunctional PC must be discussed as the main cause of this alteration.

Aged↗
PubMed1988

Influence of nitrendipine and verapamil on plasma levels, urinary excretion, and beta-blocking effect of metoprolol.

Following randomized allocation eight healthy volunteers were treated for 1 week each with metoprolol alone (100 mg twice daily), verapamil 80 mg three times a day plus metoprolol 100 mg twice daily, and with nitrendipine 20 mg twice daily. Plasma levels and urinary recovery of the beta-blocker, antipyrine clearance, and heart rate on exercise were measured. Verapamil and nitrendipine slightly prolonged elimination half-life of metoprolol. The urinary recovery of the parent beta-blocker and of its alpha-hydroxy metabolite was elevated by both calcium antagonists (verapamil and nitrendipine). Exercise tachycardia (150 beats/min without drugs) was inhibited more pronounced on the combination therapies than under metoprolol administration alone. Results of the present study indicate that calcium antagonists enhance inhibition of exercise tachycardia caused by metoprolol, possibly due to their binding to myocardial beta-adrenergic receptors which is known from the literature. As both calcium antagonists did not increase plasma levels of metoprolol, in the present study a kinetic interaction between the beta-blocker and the calcium channel blockers investigated does not appear to be responsible for the pharmacodynamic effects observed.

Adult↗
PubMed1988

Immunomodulatory properties of cimetidine in ARC patients.

The immunomodulatory potency of cimetidine, a histamine H2 receptor antagonist, was investigated in 33 AIDS-related complex (ARC) patients performing detailed immunological and clinical evaluations. Cimetidine was administered orally in daily doses of 1200 mg for a period of 5 months with an interruption of therapy after the first 3 months for an interval of 3 weeks. Significant (P less than 0.05) elevations of immunoglobulins (IgG, IgA), complement C4, B-lymphocytes, and OKT4+ (helper/inducer) cells were found after cimetidine intake. The in vitro lymphocyte proliferative response to plant mitogens was significantly increased, and the in vivo cell-mediated hypersensitivity reaction assessed by intradermal application of seven recall antigens improved significantly. These effects were both reversible with the discontinuation of cimetidine and reproducible with repeated administration of the drug. Clinical data such as performance status, body weight, and fever were influenced favorably (P less than 0.05) by cimetidine. The frequency of diarrhea and the lymph node size were also diminished significantly. The data suggest that cimetidine may at least partially restore immunofunctions in AIDS-related complex.

AIDS-Related Complex↗
PubMed1988

The influence of renal function on clinical pharmacokinetics of moxonidine.

Investigations were carried out on 24 hypertensive or borderline hypertensive patients with different degrees of renal function. Eight had normal renal function [glomerular filtration rate (GFR) greater than 90 ml/min], 8 moderate (GFR 30 to 60 ml/min) and 8 severe renal impairment (GFR less than 30 ml/min). All patients were given moxonidine 0.3mg once daily for 7 days and both pharmacokinetic and pharmacodynamic data were determined. During moxonidine treatment plasma elimination half-life, area under the plasma concentration-time curve (AUC) and apparent total clearance (CLT) showed statistically significant differences among patients in the 3 groups. Elimination half-life was 2.6 +/- 0.9 hours in patients with a GFR greater than 90 ml/min and increased to 6.9 +/- 3.7 hours in those with a GFR less than 30 ml/min (mean +/- SD; p = 0.012). Correspondingly, AUC0-24 h rose from 5.4 +/- 2.7 to 17.2 +/- 7.9 micrograms/L . h (p = 0.001), and CLT decreased from 1150 +/- 602.l ml/min to 369 +/- 227.6 ml/min (p = 0.001). These data suggest that once-daily administration of 0.3mg moxonidine may be appropriate in patients with impaired renal function. Independent of renal function, moxonidine was well tolerated in 22 of 24 patients. No deterioration in renal function as a consequence of the use of moxonidine was found. Thus, in patients with renal failure, dosage of moxonidine should be individually titrated according to the desired clinical response, as is recommended for hypertensive patients without renal impairment.

Administration, Oral↗
PubMed1988

Angiotensin-converting enzyme inhibitors. Relationship between pharmacodynamics and pharmacokinetics.

The inter-relationship between the pharmacokinetic and pharmacodynamic behaviour of ACE inhibitors is reviewed. First, some of the methods which have been used to assess the pharmacodynamics of ACE inhibitors in humans are presented. They include humoral assays (e.g. ACE activity in plasma, renin activity, etc.), haemodynamic changes (blood pressure, total peripheral resistance, etc.) and agonist challenges (angiotensin I infusions). Subsequently a pharmacokinetic-dynamic model is described, based on biochemical processes obtained after ACE inhibition, which seems to be useful for the interpretation of the complex processes. The various correlations between plasma drug concentration on the one hand and plasma ACE activity, angiotensin II concentration in plasma or blood pressure on the other, are discussed on the basis of this model. From the model obtained it becomes obvious that under many circumstances the release of the inhibitor from ACE binding is the step which in fact determines the pharmacodynamically relevant elimination rate of the drug at low concentrations, whereas at high concentrations the elimination of the drug is mainly dependent on kidney (and/or liver) elimination rate. The dynamic-kinetic correlations are then presented for some ACE inhibitors in various disease states: arterial hypertension, heart failure, old age, renal failure, liver disease. In a final section the kinetic and dynamic relevance of interactions of ACE inhibitors with food and other drugs is described (e.g. prostaglandin inhibitors, diuretics, digoxin and cimetidine). Despite the great body of literature which deals with the kinetic and/or dynamic properties of ACE inhibitors, precise knowledge of the relationship between their kinetic and dynamic behaviour is rather limited and there is a clear need for further studies to elucidate this complex topic, thereby improving therapeutic possibilities with these useful new compounds.

Aged↗
PubMed1988

[A non-specific vulvo-vagino-gingival syndrome].

The case of a 29 year-old patient is reported who initially complained about gingivitis and one year later developed a colpitis. After two years the patient was admitted to our hospital where inflammatory erosive changes of the gingiva, the vagina and the vulva were seen. Neither laboratory parameters nor histological results allowed an exact diagnosis of these findings. Also a Lichen ruber erosive had been excluded by the microscopic findings of a gingival and vaginal biopsy. Thus, the diagnosis of a non-specific vulvo-vagino-gingival syndrome was established, whereby antiphlogistic treatment with corticosteroids led to an improvement of the patient's symptoms.

Adult↗
PubMed1988

[Intrapericardial teratoma in an adult].

The intrapericardial teratoma is a very rare congenital tumor of the heart which today is mostly diagnosed in early childhood using modern imaging devices. The course of a 46-year-old male who suffered from a pericardial effusion for the first time at the age of 13 is reported. During the subsequent three decades, the patient recurrently complained of chest pains. The final diagnosis was determined following surgical removal of the tumor and upon histological evaluation. The case reported here is unique because of clinical signs and symptoms of an intrapericardial teratoma documented in adolescence and adulthood over a period of 34 years.

Adult↗
PubMed1987

[Immunologic and functional protein C determination in various internal diseases].

A new practicable and precise functional protein C evaluation test is based on the activation of protein C by a snake venom activator and determination of PC activity by its property to prolong the aPTT in a clotting assay (VK = 1.9% and 4% for intra- and interassay variance respectively). In 40 healthy controls there was a good correlation (r = 0.74) between the functional and immunological (ELISA) evaluation. In 123 patients with both evaluation methods but more pronounced with the measurement of the protein C activity a significant protein C deficiency was found in the patient groups with disseminated solid tumors, inflammatory diseases and myocardial infarction. Besides detection of hereditary PC deficiency Type II (generation of functionally abnormal PC) the functional assay profits by recording PC inhibitor complexes and otherwise dysfunctional PC in DIC. Thus, in patients with hematological neoplasias, only protein C activity was significantly decreases. Decrease of PC activity was more pronounced compared to PC Ag in liver disease indicating synthesis of functionally deficient PC, and in oral anticoagulant treatment due to detection of PIVKA-PC.

Humans↗
PubMed1987

Lupus anticoagulant associated syndrome in benign and malignant systemic disease--analysis of ten observations.

The clinical and laboratory findings in seven female patients with primary autoimmune diseases, one female patient with lymphoplasmacytoid (LP) immunocytoma and IgM paraproteinemia, and two male patients with multiple myeloma are described. The common denominator in all patients was a lupus anticoagulant or a closely related coagulation disorder. Recurrent thrombosis was observed in six patients with autoimmune diseases and in two patients with malignant monoclonal gammopathies. Other clinical manifestations included cerebral disorders (four patients with autoimmune disease/two patients with monoclonal gammopathy), repeated obstetric complications (6/1), asymptomatic valvular heart disease (6/1), renal dysfunction (6/2), hepatic involvement (2/2), and arthropathy (2/0). Laboratory investigations revealed a biologic false-positive serological test for syphilis in six patients with autoimmune disease and one with monoclonal gammopathy, antinuclear antibodies (4/0), antibodies against DNA (4/1), and a positive direct Coombs test (3/1) which was accompanied by hemolytic anemia in two patients (1/1). Additionally slight leukocytopenia (2/1) and thrombocytopenia (6/2) were observed; abnormal bleeding was only seen in one patient with severe thrombocytopenia. Other complications characteristic of LP immunocytoma or multiple myeloma were missing. The obvious similarities between the patients with autoimmune diseases and the patients with malignant monoclonal gammopathies suggest analogous pathogenetic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗