Influence of leukemia P388 on plasma concentration-time profiles of bendamustine in B6D2F1 mice.

It was the aim of this study to investigate whether leukemia P388 being an important murine transplantation tumor may alter the plasma concentration-time profiles of the alkylating antineoplastic agent bendamustine (1) in mice. In an advanced tumor stage the rapid decline of 1 plasma levels was found to be retarded in tumor-bearing in comparison to tumor-free animals both after i.v.

[2-Amino-oxazoles as potential H-bonding agents in virostatic research. 4. Pharmacokinetics and pharmacologic-toxicologic profile of 2-guanidino-4,5-dipropyloxazole hydrochloride].

Out of the group of 2-amino-oxazoles 1 was found to be the most potent antiviral compound. Following p.o.

Influence of ion-pair formation on the pharmacokinetic properties of drugs. Pharmacokinetic interactions of bretylium and hexylsalicylic acid in rabbits.

The simultaneous i.v. administration of equimolar doses of bretylium and hexylsalicylic acid results in an increase in plasma area under the curve value of both substances in comparison with their separate administration.

[Pharmacokinetics of bendamustin (Cytostasan) in B6D2F1-mice].

The pharmacokinetics of bendamustine, (1; Cytostasan), an alkylating antineoplastic agent of the N-lost group, was investigated in B6D2F1 mice. After i.v.

Influence of melanoma B16 on the pharmacokinetics of mitoguazone in mice.

In this study, the influence of different stages and transplantation routes of the experimentally widely used solid tumor melanoma B16 on the pharmacokinetics of the antineoplastic agent mitoguazone was investigated in B6D2F1 mice. It could be shown that changes of the pharmacokinetic parameters as well as the distribution pattern of this drug were clearly influenced and dependent on the tumor stage but not by the tumor inoculation route. Advanced melanoma (d16) led to a sharp decrease in the terminal elimination half-life as well as to decreased spleen levels and increased initial liver concentrations of the drug.

Influence of leukemia P388 on the pharmacokinetics of mitoguazone in B6D2F1 mice.

The aim of the present study was to investigate the influence of different stages of leukemia P388 on the pharmacokinetics of the antineoplastic agent mitoguazone in mice. It could be shown that, independent of the tumor stage investigated, the total clearance of mitoguazone is slightly reduced reflecting a moderate increase of AUC in the serum of leukemia-bearing animals. Furthermore, in an advanced tumor stage the drug levels in kidneys, liver, spleen and serum were found to be elevated to some extent in comparison to tumor-free controls in contrast to an earlier stage of leukemia.

[Kinetics of the transformation of dihydroambazone into ambazone].

The oxidation of dihydroambazone (1) by oxygen is dependent on the pH-values of the solutions used. This transformation can be inhibited and excluded, respectively, by ascorbic acid using defined concentrations. The oxidation product ambazone (2) was determined spectroscopically at different pH-values.

Influence of age on antileukemic action, subacute toxicity and tissue distribution of ambazone in B6D2F1 mice.

The influence of age of experimental animals on the antileukemic activity, toxicity and distribution of ambazone, a new potential antineoplastic agent, was studied in 2- and 12-month-old B6D2F1 mice. The predominant effect observed was a significant reduction of the antileukemic action of this compound in old-aged mice. Together with a slight increase in several toxicity parameters this caused a marked reduction of the therapeutic index in 12-month-old mice compared to younger individuals.

Distribution of cisplatin in tumor-free versus tumor-bearing B6D2F1 mice.

In healthy as well as in leukemia P388- or melanoma B16-bearing B6D2F1 mice the platinum concentrations in liver, serum and kidneys were determined after i.v. administration of 10 mg/kg cisplatin.

Influence of the ion-pair-formation on the pharmacokinetic properties of drugs. Part 5: Influence of ion-pair-formation on elimination of bretylium and hexylsalicylic acid in rats.

Following i.v. administration of the hydrophilic drug bretylium (1) and the lipophilic hexylsalicylic acid (2) in rats the plasma levels of 2 were increased due to an increased intestinal reabsorption of 2.

Age-dependent antileukemic action and suppression of immune response by 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone (ambazone) in mice.

The antineoplastic activity of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone (ambazone) against murine leukemia P388 was found to be markedly reduced in 12- and 18-month-old mice as compared to young animals. The immune response against sheep red blood cells (SRBC), a T cell-dependent antigen, was also strongly diminished in tumor-free old mice and was further suppressed after ambazone treatment. Since the antileukemic effect of ambazone disappeared more or less in congenitally athymic nude mice, in neonatally thymectomized or silica-pretreated animals, it has been concluded that the action of the compound seems to be limited to young adult immunocompetent tumor-bearing hosts.

[Mitoguazone (methylglyoxal bis(guanylhydrazone))--its status and prospects].

Because of its severe side effects, initial clinical trials of the antineoplastic compound mitoguazone (Methyl-GAG, M-G) were ceased in the middle of 1960s. One decade later pharmacokinetically guided dose schedules as well as new experimental data on the antiproliferative mechanism of action stimulated new clinical studies. First results indicated that M-G had single-agent activity against various tumors such as acute leukemia and malignant lymphoma connected with acceptable tolerance.

Pharmacokinetics of 14C-ambazone in rats.

In rats, the pharmacokinetics of 14C-ambazone after i.v. and oral administration was studied.

Distribution of 14C-ambazone in normal and leukemia P 388-bearing mice.

There is some evidence in the literature that the pharmacokinetics of anticancer agents can be influenced by the presence of a tumor. Therefore several authors recommend pharmacokinetic studies of such drugs to be performed also in tumor-bearing animals (2, 5, 7). The aim of the present study was to evaluate the influence of different stages and routes of inoculation of leukemia P 388 in B6D2F1-hybrid mice on the tissue distribution of ambazone, a new potential antineoplastic drug.

Use of alternative dose schedules for the determination of sublethal doses of potential antiviral drugs in mice.

In mice the ratio between maximally tolerated sublethal doses (MTD) after single and repeated administration of benzoxazolyl-2-formyl-S-ethyl-isothiosemicarbazone (ZIMET 111/74) was found to be different after s.c., p.

Pharmacokinetics of 3-[bis(2-hydroxyethyl)amino]acetophenone-(4,5-diphenyloxazol-2-yl) hydrazone (ZIMET 98/69) after oral administration to mice.

The pharmacokinetics of the hetarylhydrazone derivative 3H-ZIMET 98/69 after oral administration to mice were studied. The absorption of the drug is incomplete and dose-dependent; elimination proceeds slowly, the serum half-life being of about 30 h. Repeated daily administration of the drug leads to a moderate accumulation of radioactivity in serum as well as in various tissues.

The influence of dose schedules and administration routes on the toxicity of potential antiviral drugs.

The influence of two differently constructed dose schedules and of two dissimilar administration routes on the subacute toxicity of the potential antiviral drug benzoxazolyl-2-formyl-S-ethyl-isothiosemicarbazone was investigated in mice. Administration of identical aliquots of the, route dependent, maximally tolerated, dose was found to cause no significant differences in weight gain in any of the schedules used, but marked changes in lethality after oral or subcutaneous administration could be demonstrated.

[Cardiotoxic and myelosuppressive activity of various antitumor antibiotics of the anthracycline type in the rat].

The cardiotoxic and myelosuppressive effects of the potential antitumor antibiotics violamycin BI (VBI) and violamycin BII (VBII) were studied in rats in comparison with daunorubicin (DAU), doxorubicin (ADR) and carminomycin (CAR). Rats were intravenously given the compounds 10 times for three weeks at total doses of 0.4 to 3 times of the acute LD50.