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Biomedical subjects

S Kerpel-Fronius

Publications and source records attributed to S Kerpel-Fronius.

At least 55 records · Page 3Linked to original sources
PubMed1982

Metabolism and pharmacokinetics of dibromodulcitol (DBD, NSC-104800) in man--II. pharmacokinetics of DBD.

Dibromodulcitol (DBD), labelled with [3H] at position C-1, was administered orally to 6 patients in a single dose of 15 mg/kg. Kinetic parameters were calculated for the effective drug (DBD + BrEpG + DAG), protein-bound hexitol moieties and free metabolites. Approximate values were estimated for the oral bioavailability of DBD. Disposal of the drug by metabolism and excretion was described by a simplified catenary model. The results indicated that 8-20% of the drug became firmly bound to macromolecules, probably by alkylation. The slow rate of alkylation in vivo (half-life 14 hr) may imply conversion of DBD into epoxides and their alkylating interaction with the target nucleophiles. The long retention of the firmly bound hexitol moieties in the body may be an indicator of the cumulative potency of DBD and must be taken into consideration by developing dosage schedules.

Administration, Oral↗
PubMed1980

Chemical reactivity and intracavitary application of alkylating sugar alcohol derivatives.

Lycurium [1,4-di-(methylsulfonyloxy-ethylamino)-1,4-didesoxy-erythrioldimethylsulfonate; R-74; NSC-122402] undergoes rapid hydrolysis in aqueous solutions. The concentration of the alkylating compound(s), demonstrated by the 4-(4'-nitrobenzyl)pyridine reaction, decreases approximately by 80% in 10 min following the dissolution of the drug in saline. In patients peak plasma concentration of radioactivity after the intracavitary injection of 14C-labelled Lycurim is observed between 4 and 6 h. It is assumed, therefore, that only a negligible amount of pharmacologically active alkylating compounds reaches the circulation after intracavitary application. This conclusion is supported by clinical experience showing that intracavitary administration of the same amount of Lycurim causes much milder systemic side-effects than intravenous injection. A dose escalation study was started to determine the applicability of Lycurim in the form of high volume intraperitoneal instillation ('belly bath') for the treatment of ovarian cancer.

Drug Stability↗
PubMed1979

Chemotherapeutic agents and estradiol receptor binding capacity.

Cytotoxic agents used for the treatment of breast cancer did not inhibit the growth of uterus following estradiol injection to ovariectomized rats. They had no effect on the estradiol binding ability and on the dissociation constant of estradiol receptor binding of rat uterus. In addition, 1,2:5,6-dianhydrogalactitol, a highly active, proximal alkylating agent, applied in vitro did not alter the relative binding ability to tamoxifen to the cytoplasmic estradiol receptor of rat uterus and human breast cancer tissue. In summary, the present experiments did not reveal any disadvantageous interaction between simultaneously administered hormonal and cytotoxic drugs.

Animals↗
PubMed1977

Uptake of labeled dianhydrogalactitol into human gliomas and nervous tissue.

The distribution of iv administered 3H-dianhydrogalactitol (DAG) in the plasma, cerebrospinal fluid (CSF), brain, and tumor tissue was studied in 11 patients. DAG entered the CSF and was slowly eliminated, with a half-life of 20 hours. Unchanged DAG accounted for about 6%-30% of the total radioactivity in the CSF. All the tumors accumulated the drug to a higher extent than the intact white matter, except the one meningioma studied. The highest uptake was observed in the relatively benign astrocytic tumors.

Adult↗