Reference

Etoposide phosphate: what, why, where, and how?

Etoposide phosphate: what, why, where, and how?. Schacter, Lee (Department of Medicine, Divison of Medical Oncology, Yale Cancer Center, New Haven, CT, USA). Seminars in Oncology, 23(6, Suppl. 13), 1-7 (English) 1996 Saunders. CODEN: SOLGAV.In this study， 33419-42-0 and 117091-64-2 are also used. ISSN: 0093-7754. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review with 27 refs. The podophyllotoxin derivs. etoposide and teniposide are active in the treatment of a variety of malignant conditions. Both represent chem. modifications of podophyllin, an ext. of Podophyllum peltatum (May apple, mandrake, Indian apple, wild lemon, or duck's foot), a plant long used as a folk remedy and recognized in the 19th century to be effective in the treatment of cancer. While etoposide is active in the treatment of many cancers and is widely used, it has a no. of limitations due to its lack of water soly. Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-sol. prodrug of etoposide that is rapidly and completely converted to the parent compd. after i.v. dosing. The pharmacokinetic profile of etoposide after treatment with either etoposide or etoposide phosphate is identical. Toxicity and clin. activity also are the same. Because etoposide phosphate is water sol. and can be made up to a concn. of 20 mg/mL, however, it can be given as a 5-min bolus, in high doses in small vols., and as a continuous infusion. Furthermore, it is not formulated with polyethylene glycol, polysorbate 80 (Tween; ICI Americas, Wilmington, DE), and ethanol, and does not cause acidosis when given at high doses. The easier-to-use etoposide phosphate represents an improved formulation of etoposide. .

A pharmacodynamic evaluation of hematologic toxicity observed with etoposide phosphate in the treatment of cancer patients

A pharmacodynamic evaluation of hematologic toxicity observed with etoposide phosphate in the treatment of cancer patients. Kaul, Sanjeev; Srinivas, Nugehally R.; Igwemezie, Linus N.; Barbhaiya, Rashmi H. (Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA). Seminars in Oncology, 23(6, Suppl. 13), 15-22 (English) 1996 Saunders. CODEN: SOLGAV. ISSN: 0093-7754. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The pharmacodynamics of etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ), a water-sol. prodrug of etoposide, was evaluated in 39 patients with solid tumors after a 30-min i.v. infusion of escalating doses (equiv. to 50 to 175 mg/m2 of etoposide) on a day 1, 3, and 5 schedule of treatment. Serial blood samples were collected at predose and throughout the 32 h following day 1 of treatment to det. the area under the plasma concn.-time curve (AUC) of etoposide phosphate and etoposide. Hematol. profiles and serum chemistries were detd. at predose and twice weekly for approx.Several substances like 117091-64-2 may be metioned in this study. 3 wk after each treatment cycle. Both linear and nonlinear pharmacodynamic models were used to evaluate the relationship between hematol. toxicity and etoposide AUC and patient factors (age, gender, performance status, prior radiation therapy, prior chemotherapy, baseline albumin, bilirubin, alk. phosphatase, creatinine, leukocyte count, granulocyte count). Etoposide phosphate was converted rapidly to etoposide in vivo. The ratio of the etoposide phosphate AUC to that of etoposide was ￡ 1.2% indicating that etoposide was the main species in the systemic circulation. Myelosuppression was the dose-limiting toxicity, and significant decreases in white blood cell and granulocyte counts were noted. Hematol. toxicity was best described by a stepwise linear regression model consisting of etoposide AUC, serum albumin, and bilirubin. In summary, hematol. toxicity produced by the i.v. administration of etoposide phosphate correlates significantly with etoposide AUC and patient factors (baseline serum albumin and bilirubin) in cancer patients. .