Evaluation of the time-schedule dependency for the cytotoxic activity of the new vinca alkaloid derivative, S 12363 (Vinfosiltine)

European Journal of Cancer
1993.0

Abstract

S 12363 is a new vinca alkaloid derivative obtained by appending an optically active alpha-aminophosphonate at the C23 position of 04-deacetyl vinblastine. The present study concerns four different human tumour cell lines, which represent the spectrum of vinca alkaloid clinical activity. The influence of time exposure on S 12363 growth inhibition was studied in vitro. Cells were exposed to the drug during the following exposure times: 5, 15, 30 min and 1, 3, 6, 12, 24, 48, 72, 144 h. The concentrations of S 12363 applied were between 1 x 10(-2) and 1 x 10(3) nmol/l. The cytotoxic effects were assessed by using the methyltetrazolium (MTT) semi-automated test. Considering the IC50 values in terms of concentration (C) x time (T), I (C x T)50, it was shown that for an equal growth inhibitory effect (50% of cell death) the increased exposure times required higher cumulative drug exposures. More precisely, only very long exposure (greater than 24 h) resulted in very high I (C x T)50. The drug exposure ratios which correspond to I (C x T)50 values for 144 h divided by the I (C x T)50 values for 0.25 h ranged between 2.8 and 18.3. If T and C had symmetrical effects on the final growth inhibition, the I (C x T)50 ratios should have been equal to one. For all cell lines investigated there were similar dose-response curves following two types of S12363 exposure: a single day exposure or three successive daily exposures, the total C x T values being the same in both experimental situations. The basic pharmacological information provided by the present study may encourage further clinical trials of this potentially interesting new vinca alkaloid.

Knowledge Graph

Similar Paper

Evaluation of the time-schedule dependency for the cytotoxic activity of the new vinca alkaloid derivative, S 12363 (Vinfosiltine)
European Journal of Cancer 1993.0
Evaluation of the time-schedule dependency for the cytotoxic activity of the new vinca alkaloid derivative, S 12363 (Vinfosiltine)
European Journal of Cancer 1993.0
Relationship between the cellular accumulation and the cytotoxicity of S12363, a new vinca alkaloid derivative
Cancer Chemotherapy and Pharmacology 1992.0
Flow cytometric evaluation of the cell cycle perturbations induced by S12363, a new vinca alkaloid derivative
Anti-Cancer Drugs 1990.0
Phase II study of a new vinca alkaloid derivative, S12363, in advanced breast cancer
Cancer Chemotherapy and Pharmacology 1995.0
Differential in vitro action of S-12363, a new vinblastine derivative, and of its epimer on microtubule proteins
Cancer Chemotherapy and Pharmacology 1991.0
Value of early pharmacodynamic and pharmacokinetic investigations with anticancer drugs: data from phase I tolerance studies on a new vinca alkaloid derivative
Xenobiotica 1992.0
Phase I study of vintriptol, a tryptophan ester of vinblastine
European Journal of Cancer and Clinical Oncology 1991.0
Phase I study of vintriptol, a tryptophan ester of vinblastine
European Journal of Cancer and Clinical Oncology 1991.0
Kinetic Analysis of Combination Effect of Navelbine (KW‐2307) with Cisplatin against Human Lung Adenocarcinoma PC‐12 Cells in Culture
Japanese Journal of Cancer Research 1992.0