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Biomedical subjects

H K Schwabe

Publications and source records attributed to H K Schwabe.

At least 19 recordsLinked to original sources

[Roentgen microanalysis of dust particles in histologic sections of pneumoconiosis].

We investigated the significance of X-ray element analysis of histological sections obtained from 26 patients with pneumoconiosis (occupations, etc. mining, quartz processing, metal polishing, exposure to aluminium dust, exposure to asbestos dust). Aluminium-containing or, in the case of asbestosis, magnesium-containing silicates were the most commonly found minerals. Iron and titanium were detected in particular in the sections obtained from metal polishers. X-ray micro-analysis permits a more accurate determination of dust exposure, and an improvement in the description of the pneumoconiosis presenting.

Asbestosis↗

[Bronchopulmonary penetration of ciprofloxacin].

We determined ciprofloxacin levels in plasma, saliva, bronchial secretions, lavage fluid, and alveolar macrophages in 9 patients five hours following the last administration of the drug (2 x 750 mg ciprofloxacin daily over a period of at least 3 days). The ciprofloxacin concentration in the alveolar film was determined using urea as internal marker for the lavage. On average it was 2.51 micrograms/ml (= 186% of the plasma level), and clearly exceeded the minimal inhibition concentrations for the facultative pathogenic organism. This means that, in the alveolar film--which represents the barrier to descending pneumonia--an effective accumulation of the quinolone takes place.

Bacterial Infections↗

[Clinico-pharmacokinetic interactions of rifampicin, pyrazinamide and isoniazide].

We investigated the pharmacokinetic interaction of RMP (administered from the first day of treatment onwards), PZA (given from the second day onwards), and INH (day 17 onwards) in ten, previously untreated patients with pulmonary tuberculosis (five slow acetylators and five fast acetylators). In the case of the slow acetylators, higher INH and acetylhydrazine concentrations were measured than in the fast acetylators. RMP revealed the well-known autoinduction of its metabolism. During the course of continuing treatment, the PZA levels increased. No increased incidence of hepatoxic reactions was to be seen.

Chemical and Drug Induced Liver Injury↗

[Significance of the acetylator phenotype and initial oral/intravenous rifampicin administration in the treatment of tuberculosis].

In a pilot study involving 62 patients with open pulmonary tuberculosis, we established that slow acetyators and patients receiving intravenous rifampicin treatment showed a tendency towards a more rapid negativisation of the sputum culture than did fast acetyators (lower levels of isoniazid) or patients receiving oral rifampicin therapy (decreasing bioavailability of the rifampicin during treatment).

Acetylation↗

[A high pressure liquid chromatography method for detecting the isoniazid derivative isonicotinoyl-hydrazine sodium glucuronide, free isoniazid and acetylisoniazid and its use in pharmacologic studies].

A specific direct method for determining the isoniazid derivative isonicotinoyl-hydrazine sodium glucuronide (INHG-Na) with the aid of high-pressure liquid chromatography has been developed, which permits the analysis of this derivative of isoniazid in addition to isoniazid itself and acetylisoniazid in the plasma of patients. In initial pharmacokinetic applications of the method, it has been shown that plasma INHG-Na is a stable substance that liberates only negligible concentrations of INH.

Acetylation↗

Pharmacokinetics of oral and intravenous rifampicin during chronic administration.

We investigated the pharmacokinetics of rifampicin and its major metabolites, 25-desacetylrifampicin and 3-formylrifampicin, in two groups of six patients with active pulmonary tuberculosis, who received either multiple oral or intravenous rifampicin therapy in combination with intravenous isoniazid and ethambutol. Serum concentrations of rifampicin were each determined after a single oral and intravenous test dose of 600 mg rifampicin at the beginning and after 1 and 3 weeks of tuberculostatic treatment. Analysis of rifampicin and its metabolites was performed by high-pressure liquid chromatography. It was found that, due to autoinduction of its metabolizing hepatic enzymes, the systemic clearance of rifampicin increased from 5.69 to 9.03 l/h after 3 weeks of multiple dosing. The volume of distribution of the drug was constant over the period of this study. The bioavailability of the active, orally administered rifampicin decreased from 93% after the first single oral dose to 68% after 3 weeks of oral and intravenous rifampicin therapy. Relating to the increase in systemic (hepatic) clearance, a bioavailability no lower than 90% can be predicted. The reduction to 68% indicates that, in addition to an increase of hepatic metabolism, an induction of a prehepatic "first-pass" effect resulted from multiple rifampicin doses. Our study of rifampicin metabolites confirm that prehepatic metabolism was induced, since a higher metabolic ratio resulted after the oral doses than after the intravenous rifampicin test doses. A preabsorptive process can therefore be excluded as a cause of reduced bioavailability.

Administration, Oral↗