John E. Schurig

A technique for chronic jugular catheterization in the ferret

A technique was developed to provide an efficient method for blood sampling and intravenous drug administration in the ferret by using an indwelling jugular catheter.

TOXIC SIDE EFFECTS OF PLATINUM ANALOGS

Publisher Summary cis-Diamminedichloroplatinum II (cis-DDP) has been shown to be clinically effective alone or in combination against a variety of tumors such as testicular, ovarian, head and neck, and bladder. The effectiveness of cis-DDP has generated considerable interest in developing new platinum analogs with improved clinical profiles. The toxic side effects of cis-DDP include nephrotoxicity, nausea and vomiting, myelosuppression, and ototoxicity. The platinum analog programs are basically concerned with developing platinum compounds with reduced toxic side effects, especially nephrotoxicity and improved antitumor activity and spectrum. The chapter discusses a study to screen the platinum analogs for the side effects associated with cis-DDP. Side effects profiles were generated and were used in conjunction with the antitumor activity profiles to identify the most interesting analogs.

The search for more active and less toxic mitomycin and etoposide analogs

Mitomycin C has broad-spectrum activity, but clinical utility is limited by cumulative myelosuppression. VP-16 also has broad-spectrum activity and, although myelosuppression is the dose-limiting toxicity, unlike mitomycin C it is predictable and reversible. Using toxicity reduction as a target for analog selection with mitomycin C has not yet resulted in a more clinically effective agent. Another goal would be to look for more rapid recovery and reversibility of myelosuppression, or compounds with greater antitumor activity or a different antitumor profile. With VP-16, analog evaluation is in an early stage, but selection based upon increased activity not reduced toxicity appears to be the avenue of choice and has resulted in the preliminary identification of analogs which in initial studies have superior activity to the parent compound.

Pharmacokinetics of carminomycin in dogs and humans

SummaryCarminomycin was administered to four dogs and two human patients as a single intravenous dose. Plasma samples were obtained and assayed for carminomycin and carminomycinol by high pressure liquid chromatography with fluorescence detection. The plasma disappearance of carminomycin could be described by a three-compartment open model. Distribution was rapid and the apparent volume of distribution was greater than 100 l/m2 in both species. The terminal half-life of drug was 86 h in dogs and 20 h in humans. In both dogs and humans carminomycinol concentrations rapidly surpassed carminomycin levels, and terminal half-lives were longer than for the parent compound in the two species. Since carminomycinol has antitumor activity and host toxicity, this metabolite may play an important role in the efficacy and toxicity of carminomycin therapy.