PubMed Health⌕ Search

Biomedical subjects

E Fritschi

Publications and source records attributed to E Fritschi.

At least 19 recordsLinked to original sources
PubMed1995

Evaluation of the pharmacokinetics and absolute bioavailability of three isosorbide-5-mononitrate preparations in healthy volunteers.

The objective of this study was two-fold: 1. to determine the pharmacokinetic parameters and the bioavailability of two 20 mg isosorbide-5-mononitrate (CAS 16051-77-7, IS-5-MN) preparations (treatments A and B) after single oral administration and 2. to evaluate the absolute bioavailability of IS-5-MN, which was possible by the administration of a third IS-5-MN preparation (treatment C) by the intravenous route (1 mg/ml, dose 20 mg). The three preparations were examined in 24 healthy volunteers according to a randomized 3-way cross-over design, blood samples were withdrawn up to 24 h following the administration of IS-5-MN and plasma concentrations of IS-5-MN were quantified by a gas chromatography method. The two oral preparations led to peak concentration values of about 360 ng/ml of IS-5-MN in the mean 0.90 h (treatment A) and 0.97 h (treatment B) after drug administration. The corresponding values for the infusion were 339.6 ng/ml and 2.59 h in the mean. For the areas under the curve (AUC(0-infinity)) mean values of 2733 (treatment A). 2724 (treatment B) and 2877 h x ng/ml (treatment C) were found. The absolute bioavailability of both oral treatments revealed values of 95.00% and 94.74% for treatments A and B, respectively. The statistical comparison (ANOVA, confidence intervals) of the pharmacokinetic parameters showed bioequivalence between both oral preparations and equivalence in the amount of drug absorption between both oral formulations and the i.v.-infusion. The observed undesired side effects (e.g. headache or nausea) are well known to occur after IS-5-MN administration.

Administration, Oral↗
PubMed1994

Bioequivalence evaluation of two glyceryl trinitrate patches after 12-h usage in healthy volunteers.

The study objective was to determine the bioavailability and main pharmacokinetic parameters of glyceryl trinitrate (GTN, CAS 55-63-0) following cutaneous application of two different glyceryl trinitrate patches using a randomized cross-over design. The two patches investigated were Deponit 5 (a newly developed test patch) and an already marketed reference patch. Thirty-seven healthy male volunteers were included in this study; 36 of them completed the investigation. Blood samples were withdrawn up to 15 h after start of patch application and plasma concentrations of glyceryl trinitrate were quantified by a GC/MS method. For the areas under the curve from time 0 to the last quantifiable sample, AUC(O-Tlast), mean values of 1545 (test patch, n = 35) and 1686 h.pg/ml (reference patch, n = 35) were found. The corresponding peak glyceryl trinitrate plasma levels were 253 and 263 pg/ml, respectively; they were reached after 6.58 h (test patch) and 7.72 h (reference patch). The statistical comparison (ANOVA, confidence intervals) of the pharmacokinetic parameters found in the study resulted in bioequivalence of both patches. Typical side-effects known and described under glyceryl trinitrate therapy were also observed in this study.

Administration, Cutaneous↗
PubMed1994

Bioequivalence evaluation of the metabolites 1,2 and 1,3-glyceryl dinitrate of two different glyceryl trinitrate patches after 12-h usage in healthy volunteers.

In the course of this study both the bioavailability and main pharmacokinetic parameters of the glyceryl trinitrate (GTN, CAS 55-63-0) metabolites 1,2 and 1,3-glyceryl dinitrate (1,2-GDN and 1,3-GDN) were to be determined following transdermal application of a glyceryl trinitrate test patch (Deponit 5) and an already marketed reference patch. For this purpose, both patches were examined in healthy volunteers according to a randomized two-way cross-over design, blood samples were withdrawn up to 15 h after start of patch application and the plasma concentrations of both metabolites were quantified using a GC/MS method. The investigation showed the following results: Metabolite 1,2-glyceryl dinitrate: For the area under the curve from time 0 to the last quantifiable sample (AUC(0-Tlast) arithmetic mean values of 23.77 h.ng/ml (test patch) and 27.83 h.ng/ml (reference patch) were found. The corresponding peak plasma levels were 2.45 ng/ml and 2.93 ng/ml, respectively; they were reached after 6.4 h (test patch) and 8.31 h (reference patch). Metabolite 1,3-glyceryl dinitrate: The arithmetic mean values for AUC(0-Tlast) were 3.32 h.ng/ml (test patch) and 3.81 h.ng/ml (reference patch). The maximum plasma levels were 0.35 ng/ml and 0.41 ng/ml for the test and reference preparation, reached after 6.4 h and after 7.86 h, respectively. The statistical comparison (ANOVA, confidence intervals) showed bioequivalence between both patches concerning the metabolites investigated. The typical side effects known after nitrate therapy also occurred in the course of this study.

Administration, Cutaneous↗
PubMed1993

Bioavailability and pharmacokinetics of a new isosorbide dinitrate spray preparation in healthy volunteers.

In the course of this study the bioavailability and pharmacokinetic profile of a newly developed 2.5 mg (per valve release) oral isosorbide dinitrate (ISDN, CAS 87-33-2) spray preparation (Isoket Spray) were determined and compared with the results for an already marketed reference spray preparation following single application. For this purpose, the test and reference spray were examined in 18 healthy volunteers according to a randomized 2-way cross-over design. Blood samples were collected during 12 h p.a. and plasma concentrations of ISDN and its metabolites isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5-MN) were quantified by a GC-method. Both sprays showed mean maximum concentrations of ISDN in plasma of nearly 18 ng/ml about 7 min after drug intake with arithmetic mean values for the areas under the curve AUC0-12 of 7.01 (test spray) and 7.30 h.ng/ml (reference spray). For the metabolic products IS-2-MN and IS-5-MN (values for the reference spray in brackets) the corresponding maximum concentrations were 4.15 (4.21) ng/ml and 16.1 (15.9) ng/ml, respectively, and for the areas under the curve AUC0-12 values of 9.75 (9.92) h.ng/ml for IS-2-MN and 104.3 (99.7) h.ng/ml for IS-5-MN in the mean were calculated. Statistical evaluation of all pharmacokinetic parameters revealed bioequivalence between the two preparations. Typical side-effects known and described under isosorbide dinitrate therapy were also observed in this study.

Adolescent↗
PubMed1992

Evaluation of bioavailability and pharmacokinetics of two isosorbide-5-mononitrate preparations in healthy volunteers.

The objective of this study was to determine both the pharmacokinetic parameters and the bioavailability of two commercial 20-mg isosorbide-5-mononitrate (IS-5-MN) preparations (test and reference preparation) after single oral administration. For this purpose, the test and the reference preparation were examined in 24 healthy male volunteers according to a randomized 2-way cross-over design, blood samples were withdrawn up to 24 hours postadministration, and plasma concentrations of IS-5-MN were quantified by a gas chromatography (GC) method. Both preparations led to peak plasma levels of approximately 360 ng/mL IS-5-MN in the mean 0.76 hour (test) and 0.94 hour (reference preparation) after application; the plasma half-lives were about 5.2 hours, and for the areas under the curve (AUC(0-infinity)), mean values of 2741 (test preparation) and 2742 hour.ng/mL (reference preparation) were found. The statistical comparison (analysis of variance, confidence intervals) of the pharmacokinetic parameters found in the study resulted in bioequivalence of both IS-5-MN preparations. The undesired side effects/concomitant symptoms observed are known to occur after IS-5-MN administration.

Administration, Oral↗
PubMed1985

Synthesis, toxicity, and therapeutic efficacy of 4-amino-N-(2'-aminophenyl)-benzamide: a new compound preferentially active in slowly growing tumors.

The present paper describes 4-amino-N-(2'-aminophenyl)benzamide (GOE1734) with regard to synthesis; toxicity in mice, rats, and dogs; and differential therapeutic efficacy in slowly and rapidly proliferating rat tumors. GOE1734, an analog of a group of compounds known for other than antitumor effects with relatively simple N-acyl-O-phenylenediamine structure, is characterized by a low bacterial mutagenic potential after in vitro metabolic activation and DNA-DNA crosslinking activity after in vivo treatment. Maximum tolerated doses in rats and dogs amount to 4 and 1 mg/kg, respectively. High growth-inhibiting efficacy was obtained in intratibially implanted osteosarcoma, in methylnitrosourea-induced primary mammary carcinoma, and in acetoxymethyl-methylnitrosamine-induced colorectal adenocarcinoma. GOE1734 proved to be ineffective in transplanted Yoshida sarcoma and Walker 256 carcinosarcoma when single or multiple doses were administered at dose levels that were moderately toxic or not toxic. Some antitumor effects were observed in L5222 leukemia after ip transplantation, but no effect could be observed after ic implantation or in vitro incubation and subsequent retransplantation of these cells. Since the latter three rat tumors are characterized by relatively short tumor volume doubling times (0.5-2 days), whereas the first three grow slower (tumor volume doubling time, 11-19 days), the remarkable differential antitumor activity of GOE1734 in fast and slowly growing malignancies is striking.

Animals↗
PubMed1979

[Synthesis and H2-antihistaminic activity of ring methylated metiamide analogues. 4th communication: H2-antihistaminic agents (author's transl)].

In studies on structure-activity relationships of histamine H2-receptor antagonists, the influence of different imidazole ring methylation on the H2-antagonist activity was investigated. 2-Methyl-, 5-methyl-, 2,5-dimethyl- and unsubstituted analogues of metiamide were prepared and tested. While 5-methyl- and unmethylated analogues with a thiourea group proved to be quite active, the 2-methyl- and 2,5-dimethyl-derivatives, as well as those with a urea group, had only low H2-antihistaminic activity.

Animals↗
PubMed1976

Repair of the dorsal apparatus of the finger.

This paper describes a simple method of assessing the constituent features of flexion deformities of the proximal interphalangeal joints in Hansen's disease, and a simple operation to correct the anterior displacement of the lateral band and the associated contractures.

Fingers↗