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Biomedical subjects

W Kirch

Publications and source records attributed to W Kirch.

At least 217 records · Page 12Linked to original sources
PubMed1987

Simultaneous analysis of digitoxin and its clinically relevant metabolites using high-performance liquid chromatography and radioimmunoassay.

A specific assay for determining the urinary excretion of unchanged digitoxin and its metabolites is described. The procedure includes solvent extraction of urine at pH 8.5, reversed-phase high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA) of equivalent fractions. Confidence limits showed good linearity and precision of recovery and high sensitivity, accuracy and specificity. Cross-reactivities were high for digitoxigenin (DGTN) and digitoxigenin bisdigitoxoside (Bis-DGTN), they were low for digitoxigenin monodigitoxoside (Mono-DGTN) or digoxin when [125I]digitoxin RIA was used. The interference of endogenous compounds in urine in the RIA was overcome by using HPLC. Compared with results reported in the literature, the urinary recovery of unchanged digitoxin was lower, being only 8.11 +/- 1.51% of the dose administered. Amounts of 6.52 +/- 1.31% were excreted hydrolysed as Bis-DGTN, Mono-DGTN, DGTN or C12-hydroxylated as digoxin.

Adult↗
PubMed1987

[A patient with Takayasu arteritis and protein C and AT III deficiency].

A 24-year-old patient was admitted to our hospital because of vertigo, coldness and exercise-dependent pain in the left arm. She reported to have suffered from tuberculosis of the lung and a non-A-non-B hepatitis five years ago. Angiography of the aorta thoracica revealed a complete obstruction of the left arteria (a.) subclavia, stenosis of the a. carotis communis on both sides, of the a. carotis interna and the a. vertebralis on the left side as well as a non-detectable perfusion of the upper and medium segment of the left lung. ESR was elevated with 89/128 mm n.W., a hypochromic anaemia, thrombocytosis, hypalbuminaemia, elevation of alpha 2 and gammaglobulins in serum as well as a reduced quick value were found. AT III and protein C concentrations in plasma were also decreased, whereby protein C activity was reduced additionally. HLA-B-51 was positive. Takayasu's arteriitis was diagnosed by us. High-dose treatment with corticosteroids led to a considerable improvement of the clinical status and laboratory parameters of the patient. As this therapy was not associated with a normalization of protein C and AT III concentrations in plasma, protein C and AT III deficiency could be of significance in the development of Takayasu's arteriitis. Until now protein C and AT III deficiency were not described in patients with Takayasu's arteriitis.

Adult↗
PubMed1987

Bioavailability and elimination of nitrendipine in liver disease.

Twenty one patients with liver disease (cirrhosis 11, chronic hepatitis 5 and acute hepatitis 5) and 6 healthy volunteers were given a single i.v. dose of nitrendipine 5 mg. Afterwards nitrendipine 20 mg once daily were administered orally for seven days. With the intravenous injection a significant increase in the AUC and elimination half-life of nitrendipine was found in patients with cirrhosis as compared to the normal volunteers. After chronic oral dosing, the area under the plasma concentration-time curve, AUC (0-24), was 94.5 ng ml-1 h and the plasma clearance CL was 1380.6 ml/min in the healthy controls; in patients with cirrhosis the AUC (0-24) h was significantly greater at 309.4 ng ml-1 h and CL had fallen to 686.6 ml/min. Considerable accumulation of nitrendipine was also found in the patients with chronic hepatitis. Nitrendipine could not be detected in urine from any of the subjects. Blood pressure and heart rate were not significantly influenced by the treatment in the various groups investigated. Antipyrine clearance in the patients with cirrhosis was correlated with the nitrendipine plasma clearance. Thus, accumulation of nitrendipine has been demonstrated in the patients with cirrhosis and chronic hepatitis.

Administration, Oral↗
PubMed1987

Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease.

The pharmacokinetics of bisoprolol were investigated following oral administration of 10mg once daily for 7 days in 8 healthy subjects, in 14 patients with different degrees of renal impairment and in 18 patients with liver disease. In healthy subjects peak and trough steady-state concentrations of 52 micrograms/L and 11 micrograms/L, respectively, an elimination half-life of 10.0 hours and total body clearance of 14.2 L/h were observed. 5.21 mg/24 hours of unchanged bisoprolol were recovered following urinary excretion during the dosage interval. In 11 patients with renal impairment (mean CLCR = 28 +/- 5 ml/min/1.72m2) half-life was prolonged to 18.5 hours, and peak and trough concentrations were 74 and 32 micrograms/L, respectively. Correspondingly, urinary excretion decreased to 3.35 mg/24 hours and total body clearance to 7.8 L/h. In uraemic patients (CLCR less than 5 ml/min/1.73m2) the total clearance of bisoprolol was 5.0 L/h and the elimination half-life was 24.2 hours. In patients with liver cirrhosis half-life increased to 13.5 hours, steady-state peak and trough concentrations increased to 62 and 22 micrograms/L, respectively, and total body clearance decreased to 10.8 L/h. The present study indicates that in patients with impairment of kidney or liver function accumulation of bisoprolol above a factor of 2 did not occur. However, in the terminal stages of insufficiency of kidney or liver function bisoprolol dosage should not exceed 10mg.

Adrenergic beta-Antagonists↗
PubMed1987

Nitrendipine/digoxin interaction.

The effect of nitrendipine in two different dosages on digoxin plasma levels, urinary recovery, and systolic time intervals was investigated in eight healthy volunteers. Following an adequate loading dose of the glycoside, 0.25 mg digoxin twice daily was given alone for 2 weeks orally. After that, 0.25 mg digoxin twice daily was administered for two 1-week periods combined with nitrendipine, 10 mg or 20 mg once daily. The study was completed with a second digoxin monotherapy phase lasting seven days. Nitrendipine, 20 mg daily, led to a significant increase of the digoxin plasma concentration and of its area under the plasma concentration-time curve (AUC0-12) compared with digoxin monotherapy. Thus, AUC0-12 was 9.7 +/- 0.75 ng ml-1 h (X +/- SEM) when digoxin was given alone and was 11.2 +/- 0.92 ng ml-1 h under coadministration of the calcium antagonist (p less than 0.05). Nitrendipine in the dosage of 10 mg once daily caused a small, insignificant tendency to elevate digoxin plasma levels. In conclusion, nitrendipine, 20 mg daily, causes a significant increase of digoxin plasma concentration and of its AUC, which in certain patients might be of clinical relevance.

Adult↗
PubMed1986

Dose-dependence of the nifedipine/digoxin interaction?

The dose-dependence of the nifedipine/digoxin interaction was investigated in seven healthy volunteers. After an adequate loading dose of digoxin for two weeks, 0.25 mg digoxin was given alone orally twice daily. Afterwards, 0.25 mg digoxin was administered twice daily for three one week periods combined with capsules of nifedipine 5 mg, 10 mg or 20 mg (ADA-LAT) respectively on a three times daily basis. Subsequently the study was completed with a digoxin monotherapy phase lasting seven days. All three doses of nifedipine administered led to a significant increase of the digoxin plasma concentrations and of the area under the plasma concentration-time curve (AUC) compared with digoxin monotherapy. In conclusion, nifedipine causes a slight but significant increase of digoxin plasma concentrations and of its AUC (15%). This effect was not dependent on the nifedipine dose administered.

Adult↗
PubMed1986

Effect of two different doses of nitrendipine on steady-state plasma digoxin level and systolic time intervals.

The effect of two different doses of nitrendipine on plasma digoxin levels, urinary recovery and systolic time intervals was investigated in 8 healthy volunteers. Following a loading dose, digoxin 0.25 mg b.d.p.o. was given alone for 2 weeks. Then 0.25 mg digoxin b.d. was administered for two 1-week periods combined with nitrendipine 10 mg or 20 mg once daily. The study was completed with another digoxin monotherapy phase lasting 7 days. Nitrendipine 20 mg daily led to a significant increase in plasma digoxin levels and in its area under the plasma concentration-time curve AUC (0-12) was 9.7 ng ml-1h when digoxin alone was given and 11.2 ng ml-1h on co-administration of the calcium antagonist. Urinary recovery and renal clearance of digoxin were slightly but not significantly increased by nitrendipine. Nitrendipine 10 mg once daily caused a small, insignificant tendency to elevate the plasma digoxin level. Nitrendipine co-administration (10 and 20 mg once daily) did not significantly alter systolic time intervals, as non-invasively measured haemodynamic parameters, compared to digoxin treatment alone. Thus, nitrendipine 20 mg daily caused a significant increase in plasma digoxin concentrations and in its AUC, which would rarely be of clinical relevance.

Adult↗
PubMed1986

Penbutolol Pharmacokinetics: the influence of concomitant administration of cimetidine.

A possible interaction of penbutolol and cimetidine was investigated in healthy volunteers treated orally for 7 days. The plasma levels of unmetabolized penbutolol showed a slight but non-significant increase. The biphasic elimination kinetics of penbutolol (half-lives 0.8 and 17 h) was not affected by coadministration of cimetidine. Plasma levels of penbutolol were not significantly altered by chronic treatment with cimetidine, whereas the levels of 4-hydroxypenbutolol and 4-hydroxypenbutolol glucuronide were significantly reduced.

Adult↗