Biomedical subjects
Publications and source records attributed to J E Strong.
A case is presented of a patient who ingested a potentially fatal dose of phenylbutazone. Her clinical condition deteriorated despite adequate supportive therapy and the use of charcoal haemoperfusion proved life-saving.
The pharmacokinetics of bleomycin were studied after im injection in patients with malignant lymphoma. Mean peak serum concentrations of 0.133, 0.326, and 0.587 milliunits/ml were obtained approximately 1 hour after injection of 2, 5, and 10 units/m2, respectively. The mean half-life was 155 minutes, with a range of 65--235 minutes. Thirty-three percent of the administered dose was recovered in the urine after 4 hours. The urinary excretion of bleomycin was 61% during the 24 hours after injection, with some variability that was not explained by differences in dose or creatinine clearance.
The pharmacokinetics of tallysomycin, a third-generation bleomycin analog, and bleomycin have been determined and compared in the beagle dog. Both compounds exhibited biphasic plasma elimination characteristics and were extensively absorbed after in injection. The elimination half-lives of tallysomycin after iv and im administration were 1.51 +/- 0.41 hours and 2.40 +/- 0.667 hours respectively. These values were longer than the comparable iv (1.01 +/- 0.19 hours) and im (1.12 +/- 0.39 hours) elimination half-lives for bleomycin. The volume of distribution in the central compartment after iv administration was 0.111 +/- 0.039 liter/kg for tallysomycin and 0.125 +/- 0.0723 liter/kg for bleomycin. The total apparent volumes of distribution were 0.706 +/- 0.255 liter/kg and 0.388 +/- 0.245 liter/kg for tallysomycin and bleomycin respectively after iv injection. These values were significantly different (P less than 0.05). Total urinary recovery in 24 hours for tallysomycin was significantly (P less than 0.05) less than that for bleomycin after both iv and im injections. These observed differences in pharmacokinetic behavior may, in part, account for differences in in vivo antitumor activities and toxic effects which have been reported for these drugs.
Antibodies were raised against a new antineoplastic agent, tallysomycin, for use in a radioimmunoassay. The assay was sensitive to 2.5 ng of tallysomycin, had a coefficient of variation of 10.5% at 50 ng/ml, and was highly specific for tallysomycin A. The antibody exhibited reduced cross-reactivity with closely related tallysomycin analogs and little or no immunoreactivity with other antitumor antibiotics including bleomycin and phleomycin. Increased immunoreactivity occurred following copper chelation of tallysomycin B as compared with the non-chelated forms, thus indicating possible conformational alterations upon metal binding.