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Biomedical subjects

G Franke

Publications and source records attributed to G Franke.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetic interactions between isoniazid and theophylline in rats.

Pharmacokinetic interactions between isoniazid and theophylline were studied in male Wistar rats, 206 +/- 17 g. Concomitant oral administration of 2 x 5 mg kg-1 isoniazid accelerated slightly the disposition of theophylline (10 mg kg-1, i.v.) whereas 2 x 25 mg kg-1 isoniazid slowed it marginally. The differences in distribution volume, systemic clearance and area under the concentration-time curve (AUC) between the high and the low dose, however, were statistically significant. One week pretreatment with 10 mg kg-1 isoniazid tended towards inhibition (significant decrease of systemic clearance, increase of AUC) and 50 mg kg-1 to acceleration (decrease of half-life, mean residence time and AUC, increase of systemic clearance) of theophylline disposition. After oral pretreatment with 20 mg kg-1 theophylline, neither the kinetics of free isoniazid (50 mg kg-1, i.v.) and the amount acetylated nor the acetylation indices differed from the controls. There was no evidence that concomitant or subacute administration of different doses of isoniazid affects major metabolic pathways of theophylline or that prolonged theophylline treatment interacts with the N-acetylation capacity.

Animals↗
PubMed1992

Effects of isoniazid on hepatic drug oxidation and N-acetylation capacities in rats.

In vitro and in vivo activity of hepatic monooxygenase as well as in vivo N-acetylation capacity were assessed in male Wistar rats after oral pretreatment with 10 and 50 mg/kg isoniazid for 7 d. Both doses of isoniazid showed no statistical difference in protein contents, total cytochrome P-450 and the activities of aminopyrine N-demethylase as well as ethoxyresorufin-O-deethylase in the 9000 x g liver homogenate suspension compared to the saline pretreated group. Body and relative liver weights remained also unchanged. In vivo isoniazid pretreatment with either dose hardly changed the kinetic profiles and parameters of phenazone and sulfadimidine (free + total). The results suggest that drug metabolizing pathways that can be evaluated by the metabolism of the model substances employed here may not be modified by prolonged isoniazid treatment.

Acetylation↗
PubMed1992

Bioavailability of metronidazole formulations (Vagimid).

The bioavailability of metronidazole (0.5 g) from Vagimid tablets and dragées were compared with tablets of a reference formulation in 12 male healthy volunteers (age 20-32 years, body weight 61-77 kg). Metronidazole and its two main oxidized metabolites in serum were determined quantitatively with an hplc method. Metronidazole from Vagimid tablets was absorbed more rapidly than from the reference but at the same extent of absorption. The pharmacokinetic profile of Vagimid dragées was similar to the behaviour of the reference but AUC of dragées was slightly but significantly lower. All elimination parameters of metronidazole as well as the formation of the two metabolites were not different after administration of the oral formulations.

Adult↗
PubMed1991

Drug oxidation and N-acetylation in rats pretreated with subtoxic doses of streptolysin O.

SLO in sublytic doses (100 HU/kg body wt) depressed the hepatic microsomal cytochrome P450 and aminopyrine-N-demethylase but increased significantly the cytosolic N-acetyltransferase after acute and subacute (5 days) pretreatment of male Wistar rats. Aniline hydroxylase was reduced after acute and unchanged after subacute pretreatment. The effects of SLO on the oxidative enzymes and drug N-acetylation might have been caused by the membranal and immunological properties of the toxin.

Aniline Hydroxylase↗
PubMed1991

Immunotherapy of murine visceral leishmaniasis with murine recombinant interferon-gamma and MTP-PE encapsulated in liposomes.

The efficiency of immunotherapy with murine recombinant interferon-gamma (rIFN-gamma) in mouse visceral leishmaniasis caused by Leishmania donovani was examined. To avoid the side effects encountered after the in vivo administration of high dosages of free IFN-gamma, this lymphokine and muramyltripeptide (MTP-PE) were encapsulated into multilamellar liposomes. We established that a combination of 5 X 10(3) U of IFN-gamma and 6 micrograms of MTP-PE, encapsulated in liposomes and given i.v. in C56BL/6 and BALB/c mice activates macrophages from spleen and liver in vivo to kill L. donovani in vitro. Neither empty liposomes nor the same concentration of free IFN-gamma and/or MTP-PE injected i.v. resulted in a leishmanicidal activity of these macrophage populations. For verification of these results in an in vivo infection model, susceptible mice were infected with L. donovani and were treated with IFN-gamma and MTP-PE encapsulated in multilamellar vesicles. Treatment consisted of multiple i.v. injections beginning 4 and 2 days before infection (prophylactic), either simultaneously with the infection or at various times of the exacerbation and remission phases of visceral leishmaniasis. These mouse strains treated with IFN-gamma and MTP-PE in liposomes had significantly fewer splenic parasites than untreated mice or control animals treated with free drugs or empty liposomes. The targetting of multilamellar vesicles to liver and spleen make them particularly suited for the delivery of macrophage-activating substances used for treatment of visceral L. donovani infection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

N-acetylation and debrisoquine hydroxylation polymorphisms in patients with Gilbert's syndrome.

1. N-acetylation and debrisoquine hydroxylation phenotypes were determined in 54 patients with Gilbert's syndrome and in 247 (sulphamethazine) and 76 (debrisoquine) non-related healthy volunteers. 2. Forty (74.1%) of the patients and 135 (54.7%) of the healthy volunteers were slow acetylators (chi 2 = 6.87). In the patients, the cumulative urinary excretion of sulphamethazine up to 6 h (Ae(0,6)) was significantly lower. No differences in the frequency of debrisoquine poor metabolizers were observed: Gilbert's syndrome 5/54 (9.3%), healthy volunteers 5/76 (6.6%). The metabolic ratios were similar in both groups as well as the urinary recoveries of debrisoquine and its 4-hydroxy metabolite. 3. Gilbert's syndrome seems to be related in some way to N-acetylation but not to the debrisoquine hydroxylation polymorphism.

Acetylation↗
PubMed1991

N-acetylation and oxidative capacity in aged volunteers determined with sulfamethazine and antipyrine.

The elimination of antipyrine (AP 15 mg/kg) and sulfamethazine (SM 500 mg) was measured in healthy volunteers of rapid and slow acetylator phenotype. Nineteen males were 20-32 years of age, 11 males and 6 females between 62-86 years of age. Apparent volume of distribution of AP was reduced in advanced age independent of the acetylator status of the individuals. Total body clearance was significantly lower and half-time and mean residence time were higher only in slow but not in rapid acetylators. In the elderly of both phenotypes, the acetylation ratios of SM were significantly enhanced. Renal and metabolic clearance were decreased and AUC-values of SM and its acetylated metabolite were increased in slow but unchanged in rapid acetylators. Physiological peculiarities of distribution and renal excretion of SM and its acetylated metabolite in advanced age may have caused the contradictory results.

Acetylation↗
PubMed1991

Pharmacokinetics of almitrine in healthy volunteers and patients with essential hypertension.

Pharmacokinetic studies with the arterial chemoreceptor stimulant almitrine (100 mg per os) were performed in 12 healthy volunteers and 8 patients with essential hypertension stage I in order to evaluate the suitability of the drug for physiological tests. The parent compound was determined gas-chromatographically. Almitrine was absorbed with maximal serum levels after 1.8 +/- 0.4 h in healthy volunteers and 1.5 +/- 0.3 h in patients. The elimination proceeded biexponentially with terminal half-lives from 14.6 to 43.4 h in volunteers and 12.5-45.0 h in patients. Further characteristics were large distribution volumes (16.1 +/- 4.5 ml/g in healthy volunteers, 13.9 +/- 4.7 ml/g in patients) and large interindividual variations of all pharmacokinetic parameters by a factor of 2 to 6. Significant differences between healthy individuals and patients were not observed. The drug was well tolerated. The pharmacokinetic properties of almitrine should be included into its evaluation as a test compound.

Administration, Oral↗
PubMed1991

[Serum hyposomolarity, brain edema and the bulbar brain syndrome as complications in the course of severe cranio-cerebral injuries in children].

It is reported on a severe craniocerebral trauma in a child with a rarely occurring spontaneously induced serum hypoosmolality which led to brain edema combined with intracranial increase of pressure and bulbar brain syndrome. By means of bedside brain ventricle catheterization for liquor drainage following drill-hole trepanation, the complication could be controlled. Later the recovery was completed under supervision of the outpatient department. Pathophysiological metabolic peculiarities, especially osmolality, are discussed. The necessity of special and repeated controls of the metabolic characteristics osmolality, sodium and potassium in serum and urine as well as the water and sodium balance within 24 hours is emphasized.

Brain Edema↗
PubMed1990

N-acetylation and debrisoquine type oxidation polymorphism in Caucasians--with reference to age and sex.

Phenotypes of the N-acetylation and debrisoquine type oxidation polymorphism were determined with sulfamethazine and debrisoquine in 145 healthy volunteers (31-80 years, 64 males, 81 females) of a North-East German area. Seventeen (11.7%) were poor metabolizers of debrisoquine and 81 (55.9%) slow acetylators of sulfamethazine. No significant correlations between the frequencies of oxidation and acetylation phenotypes, age, and sex were found. Only a tendency of rapid acetylators to accumulate among individuals above 60 years was noticed. Parameters of phenotyping were not influenced by sex. With age, metabolic ratios of N-acetylation but not of oxidation phenotyping increased. The urinary excretion (0-8 hours) of debrisoquine, sulfamethazine and their metabolites was strikingly reduced in the elderly. Misclassifications of acetylation phenotyping cannot be excluded because of the age dependent kinetics of the test drug.

Acetylation↗
PubMed1990

Oxidation phenotyping with debrisoquine in Germany (East).

An hplc method is described which determines debrisoquine and its metabolite, 4-hydroxydebrisoquine, quantitatively after conversion of the guanidine moieties into the corresponding pyrimidines. Sensitivity, precision, and accuracy have been sufficient enough for the reliable hydroxylation phenotyping of 145 non-related healthy volunteers (64 males, 81 females, 31-80 years). 17 (11%) were poor metabolizers of debrisoquine (gene frequency: 34.2%).

Adult↗
PubMed1990

Tryptophan metabolic studies in patients with presenile cataracts.

In 43 patients with presenile cataracts an oral tryptophan loading test with 5 g L-tryptophan was performed and the 24-hour urinary excretion of kynurenine and xanthurenic acid was determined. 5 cases showed pathological deviations and an excretion pattern of tryptophan metabolites via kynurenine, similar as in vitamin B6-dependent xanthurenic aciduria.

Adolescent↗