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Biomedical subjects

W Kirch

Publications and source records attributed to W Kirch.

At least 253 records · Page 14Linked to original sources
PubMed1985

Effect of rifampicin treatment on hepatic drug metabolism and serum bile acids in patients with primary biliary cirrhosis.

Six patients with primary biliary cirrhosis (PBC) were treated with a daily oral dose of 600 mg rifampicin for 2 weeks to induce the hepatic metabolism of drugs and bile acids. On rifampicin 5 of 6 patients experienced a pronounced decrease of their pruritus. In all patients the oxidative cytochrome P-450 dependent drug metabolism was induced as shown by an increase of antipyrine-clearance from 36.3 +/- 8.8 to 80.6 +/- 20.1 ml/min and an enhanced urinary excretion of 6-beta-hydroxycortisol from 454 +/- 1.99 to 1607 +/- 362 micrograms/24 h. Furthermore, in all 6 patients the serum alkaline phosphatase declined. In the 3 cholestatic patients (bilirubin greater than 1.0 mg/dl) the serum concentration of total and conjugated bile acids was strikingly reduced. Thus, rifampicin is an inducer of hepatic metabolism in PBC-patients, ameliorates the pruritus and can lower serum concentrations of alkaline phosphatase and bile acids.

Adult↗
PubMed1985

Isolation of human hepatic microsomes and their inhibition by cimetidine and ranitidine.

Human hepatic microsomes were isolated from wedge biopsies of the liver from 13 patients undergoing abdominal surgery. Ultrasonic homogenisation was used to increase the yield of microsomal monooxygenase activity (7-ethoxycoumarin O-deethylase, NADPH-cytochrome c reductase), resulting in a 30% higher total enzyme activity per g liver than preparation by other techniques. In 4 individual microsomal preparations the influence of cimetidine and ranitidine on Michaelis-Menten kinetics of O-deethylation and of reductase activity were studied. Without the H2-receptor blocking drugs, enzyme kinetics of O-deethylation with a Km of 51.0 +/- 16.4 microM (n = 3) were obtained using Lineweaver-Burke plots. Both, cimetidine and ranitidine inhibited the O-deethylation; cimetidine had a five-fold higher inhibitory affinity (Ki 1.01 and 3.94 mM) to the monooxygenase than ranitidine (Ki 4.96 and 17.70 mM) in the uninduced liver. However, in liver from a patient with induced enzyme activity (Km = 478.0 microM), the Ki of ranitidine was similar to that of cimetidine (Ki ran 3.57 versus Ki cim 2.49 mM). The reductase activity was not inhibited by ranitidine and only marginally so by cimetidine. The results suggest that in human hepatic microsomes oxidative drug metabolism is inhibited by both H2-receptor antagonists. However, the inhibitory potency of the compounds seems to depend on the individual isozyme pattern of the hepatic microsomes. Thus, while cimetidine is an relatively nonspecific enzyme inhibitor, ranitidine might more selectively inhibit induced drug metabolizing enzymes.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1984

[The Behçet syndrome. Report on 12 cases and overview of the literature].

Based on a description of the disease in 12 patients (six German, five Turkish and one Yugoslav) the symptoms and diagnostic criteria of Behçet's syndrome are explained. Regional differences in sex distribution, differences in the symptomatology of female and male patients, severe vascular complications, and lymphoproliferative disorders in the advanced stages receive particular mention. In the absence of specific laboratory findings, diagnosis and assessment of disease activity depend primarily on clinical criteria. The present conception of the etiology yields several therapeutic regimens, though their efficacy is difficult to evaluate due to spontaneous remissions and exacerbations.

Adolescent↗
PubMed1984

The influence of two histamine H2-receptor antagonists, cimetidine and ranitidine, on the plasma levels and clinical effect of nifedipine and metoprolol.

In six healthy volunteers pharmacokinetic and pharmacodynamic interaction of metoprolol and nifedipine with cimetidine and ranitidine was investigated after 1 week of monotherapy with nifedipine and metoprolol and after 1 week each of combined treatment of these drugs with the H2-receptor antagonists. Ranitidine led to a 50% increase in mean peak plasma levels and in the area under the plasma level time curve (AUC) of metoprolol (p less than 0.05) and to an insignificant 30% rise in these parameters of nifedipine (p less than 0.05). Cimetidine increased metoprolol's peak plasma levels of AUC by about 60% (p less than 0.05) and those of nifedipine by 80% (p less than 0.05). Compared to monotherapy with metoprolol beta blocking activity measured by exercise induced tachycardia was not significantly stronger inhibited under the combined treatment of metoprolol with each of the two H2-receptor antagonists. On the other hand the antihypertensive effect of nifedipine was significantly increased during concurrent administration of cimetidine in seven hypertensive patients when compared with monotherapy.

Adult↗
PubMed1984

The interaction between H2-receptor antagonists and beta-adrenoceptor blockers.

The degrees of interactions between the H2-receptor antagonists, cimetidine and ranitidine, and several beta-adrenoceptor blockers were investigated in healthy volunteers following 7 days of oral monotherapy with penbutolol, propranolol, metoprolol, pindolol and atenolol, and after co-administration with each of the H2-receptor antagonists. The kinetic parameters of unmetabolised penbutolol and penbutolol glucuronide were unaffected, whereas the levels of 4-hydroxypenbutolol and 4-hydroxypenbutolol glucuronide were significantly reduced. Furthermore, cimetidine led to a marked increase in propranolol and metoprolol plasma levels. During co-administration with cimetidine, pindolol plasma levels were only slightly raised, whereas the pharmacokinetics of atenolol were not affected. With regard to pharmacodynamics, the inhibition of exercise-induced tachycardia by each of the beta-adrenoceptor blockers was not affected by cimetidine. Ranitidine did not alter atenolol plasma levels, but did raise the peak plasma concentration of metoprolol by about 30%. It is concluded that cimetidine interactions do occur and can be predicted for substances metabolised by the cytochrome P-450 pathway.

Adrenergic beta-Antagonists↗
PubMed1984

Interaction between the beta-adrenoceptor blockers metoprolol and atenolol with amitriptyline and their effects on oxidative liver metabolism.

Neither the kinetics of the hydrophilic beta-adrenoceptor blocker atenolol nor those of the lipophilic metoprolol were influenced by the concurrent administration of amitriptyline. Compared with placebo, chronic administration (14 days) of atenolol and metoprolol (each as monotherapy) did not significantly reduce oxidative liver metabolism as measured by antipyrine half-life and by 6-beta-hydroxycortisol excretion. Compared with atenolol and metoprolol monotherapy, chronic administration of amitriptyline concurrently with each of the beta-adrenoceptor blockers produced an insignificant decrease (circa 10-20%) in antipyrine half-life and 6-beta-hydroxycortisol excretion. Amitriptyline appears therefore to have little enzyme-inducing activity.

Adult↗
PubMed1984

Pharmacokinetic and pharmacodynamic interactions between phenprocoumon and atenolol or metoprolol.

Pharmacological interactions in both directions between phenprocoumon and atenolol and metoprolol were investigated using a crossover trial. Co-administration of phenprocoumon did not significantly affect Cmax, tmax, t1/2,22, AUC for atenolol or metoprolol. Co-administration of metoprolol, but not atenolol, increased mean plasma phenprocoumon concentrations 4 and 6 h after dosing and was caused by a decrease in the apparent volume of distribution. This increase in plasma phenprocoumon was not associated with an increase in prothrombin time or in the total area under the concentration-time curve. Although the transient increase of phenprocoumon plasma levels caused by metoprolol may be of little clinical significance after a single dose of phenprocoumon, a more important alteration in phenprocoumon disposition and effect should be considered in individual patients on long-term therapy.

4-Hydroxycoumarins↗
PubMed1984

Drug interactions with nitrendipine.

Interactions between calcium channel blockers like nifedipine and concurrently administered drugs like digoxin or cimetidine have been described in the literature. Therefore, possible interactions of the new calcium channel blocker nitrendipine (20 mg daily) with digoxin (0.5 mg daily), digitoxin (0.1 mg daily), cimetidine (1,000 mg daily), ranitidine (300 mg daily), atenolol (100 mg daily), metoprolol (200 mg daily), and acebutolol (400 mg daily) were studied following 1 week of combined treatment of nitrendipine with each of these drugs. Six healthy volunteers were investigated (mean age, 30.2 +/- 2.1 years; mean body weight, 69.7 +/- 4.7 kg; means +/- SEM). Under nitrendipine monotherapy, maximum plasma levels (Cmax) averaged 41.6 +/- 12.8 ng/ml, and they were reached after 2 h. Mean area under the curve was 131.5 +/- 40 ng ml-1 h, and "oral" plasma clearance (Clpl) amounted to 80.8 +/- 27.5 L/h. The H2 receptor antagonists cimetidine and ranitidine and the digitalis glycosides like digoxin or digitoxin did not alter nitrendipine kinetics significantly. Also simultaneous treatment with beta-blockers did not significantly influence kinetic values of the calcium channel blocker, but atenolol showed a tendency to increase Cmax of nitrendipine to 54.2 +/- 19.7 ng/ml, when its Clpl was distinctly lowered to 42.7 +/- 10.4 L/h (p greater than 0.05 compared with 80.8 +/- 27.5 L/h under nitrendipine monotherapy). Increased digoxin plasma levels and digoxin-induced side-effects were seen under nitrendipine co-administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1984

Clinical pharmacokinetics of nimodipine in normal and impaired renal function.

Twelve patients with different degrees of renal function were investigated. Six of them had moderately impaired renal function (glomerular filtration rate-GFR 20-60 ml/min) and six were preuraemic (GFR less than 20 ml/min). Patients received a single oral dose of 30 mg nimodipine on the first and eighth day, from the second to the seventh day they received 30 mg thrice daily. The results of this study were compared with the data of a similar study with six healthy volunteers (GFR greater than 90 ml/min) who also received for one week nimodipine 40 mg three times daily. In these subjects peak plasma levels of nimodipine ranged between 15.5 and 106.7 micrograms/1 on first treatment day and did not differ significantly from those on the 7th day of therapy ranging between 17.0 and 80 micrograms/1. Mean terminal elimination half-life of nimodipine was 2.77 +/- 0.46 h in normal renal function, but was 22.23 +/- 6.94 h in patients with impaired renal function (12 patients with GFR less than 60 ml/min). The mean area under the plasma level time curve (AUC) with 541.5 +/- 16.93 ng ml-1 h increased in patients with renal insufficiency compared to those with normal renal function (74.65 +/- 9.44 ng ml-1 h). Dosage adjustment of nimodipine appears to be necessary in renal failure.

Adult↗
PubMed1983

[Effect of cimetidine and ranitidine on the pharmacokinetics and anti-hypertensive effect of nifedipine].

Simultaneous administration of cimetidine and nifedipine to six healthy volunteers produced an about 80% rise in maximal plasma levels and the area under the plasma level-time curve of nifedipine compared with results on nifedipine administration alone (P less than 0.05). After treatment for one week with 4 X 10 mg nifedipine daily and 3 X 200 mg cimetidine daily and 400 mg at night plasma level peaks of nifedipine averaged 87.7 +/- 19.1 ng/ml, while after 4 X 10 mg nifedipine alone they were only 46.1 +/- 10.6 ng/ml. Ranitidine produced an approximately 25%, nonsignificant, rise in plasma level-time curve and peak plasma levels of nifedipine. Seven hypertensives (WHO stage I and II) had a mean arterial blood pressure level of 127 +/- 2.5 mm Hg after two-week placebo administration, and of 109 +/- 2.38 mm Hg after four weeks of nifedipine alone at 4 X 10 mg daily (P less than 0.01). After additional administration of 1 g cimetidine daily for two weeks the mean blood pressure fell significantly to 95 +/- 3.1 mm Hg (P = 0.02), while blood pressure fell to 103 +/- 3.88 mm Hg after two weeks of additional administration of 300 mg ranitidine daily, a fall which was not significant (P greater than 0.05). The interaction of nifedipine and cimetidine is thus of clinical significance because of its pharmacodynamic effect.

Adult↗
PubMed1983

Clinical experience with atenolol in patients with chronic liver disease.

The pharmacokinetics of atenolol were investigated following single intravenous (25 mg) and oral administration (100 mg) of atenolol in 13 patients with chronic liver disease and normal renal function and in 12 normal healthy volunteers. Four of the patients with chronic liver disease were not included in the statistical evaluation of kinetic data, since a reduction of creatinine clearance was observed during the course the study after ingestion of atenolol. A tendency to an increased distribution volume of atenolol could be observed in subjects with liver disease compared to normal volunteers. After intravenous and oral administration of atenolol, pharmacokinetic parameters such as elimination half-life, plasma clearance, and renal clearance did not differ significantly between patients with chronic liver disease and healthy volunteers. Thus, plasma half-life after intravenous dosing of atenolol was 6.0 +/- 0.46 hours in patients with hepatic disease and 5.0 +/- 0.4 hours in the controls, indicating absence of atenolol accumulation in hepatic failure. In the first days after starting beta-blocker therapy such as atenolol administration, parameters of kidney function as plasma creatinine, or possibly creatinine clearance, should be initially monitored at regular intervals, as there may be transient changes of renal function in patients with chronic liver disease, leading to delayed elimination of the drug.

Administration, Oral↗
PubMed1983

Accumulation and adverse effects of metoprolol and propranolol after concurrent administration of cimetidine.

Pharmacokinetics of metoprolol, propranolol and atenolol were investigated in six healthy volunteers following 7 days of oral monotherapy with these drugs and after 7 days concurrent administration of each of these betareceptor antagonists with cimetidine. Application of cimetidine did not lead to any interaction with atenolol, whereas mean peak plasma levels of metoprolol were increased by 70%, and those of propranolol by 95% due to concurrent administration of cimetidine (p less than 0.05). The AUC of the two last mentioned beta blockers behaved similarly (p less than 0.05). Measurement of exercise-induced tachycardia on the 6th day of administration showed no differences between monotherapy with the beta blocker and combined treatment with each of them and cimetidine. Except for one volunteer who complained of anxiety, weakness and sweating on the 6th day of cimetidine/metoprolol administration, no adverse effects could be observed during the combination therapy with cimetidine and the beta blockers or in monotherapy with beta blockers.

Adult↗
PubMed1983

Atenolol interaction with aspirin, allopurinol, and ampicillin.

Atenolol kinetics were investigated in six healthy subjects after 100 mg orally, as monotherapy a 6-day treatment began 48 hr later. After a therapy-free interval of 4 wk, the same subjects received the same dose of atenolol with 1 gm ampicillin, 500 mg aspirin, and with 300 mg allopurinol. Allopurinol and aspirin did not substantially alter the kinetics of atenolol. After a single oral dose of 100 mg atenolol combined with 1 gm ampicillin, the bioavailability of atenolol was reduced to 36 +/- 5% compared to 60 +/- 8% after monotherapy. During long-term treatment with atenolol and ampicillin the bioavailability of atenolol fell to 24% (P less than 0.01). Mean peak plasma levels were lowered from 511 +/- 59 ng/ml on monotherapy to 344 +/- 33 ng/ml after the combination with ampicillin. The area under the plasma level-time curve, mean steady-state concentration, and urinary recovery were reduced, also. Twelve hours after 100 mg atenolol and 1 gm ampicillin, exercise tachycardia was significantly higher than after atenolol alone. During the 4-wk treatment in six hypertensive patients blood pressure levels of those on atenolol alone were not different from those on the combination therapy with ampicillin.

Adult↗