Similar articles

Abstract: To determine the pharmacokinetics of gemcitabine (2′,2′-difluorodeoxycytidine) in Chinese non-small-cell lung cancer (NSCLC) patients. Six study subjects were administered gemcitabine at a fixed dose rate of 10 mg/m² per min (1200 mg/m², two hours infusion), and carboplatin and plasma gemcitabine concentrations were measured by ion-pair reversed-phase high-performance liquid chromatography (HPLC). 3P97 Pharmaceutical Kinetics Software was used for the calculation of pharmacokinetic parameters. The obtained mean parameters, elimnation half life (t_1/2) (10.67±3.38 min), area under the curve (AUC) (7.55±1.53 (µg·h)/ml), and clearance (CL) (3940.05±672.08 ml/min), were consistent with those reported in literature. The hematologic toxicology result showed that the regimen was effective on and tolerated by the patients.

[1] Abbruzzese, J.L., Grunewald, R., Weeks, E.A., Gravel, D., Adams, T., Nowak, B., Mineishi, S., Tarassoff, P., 1991. A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. J Clin Oncol, 9(3):491-498.

[2] Abratt, R.P., Bezwoda, W.R., Falkson, G., Goehals, L., Hacking, D., Rugg, T.A., 1994. Efficacy and safety profile of gemcitabine in non-small cell lung cancer: a phase II study. J Clin Oncol, 12(8):1535-1540.

[3] Anderson, H., Lund, B., Bach, F., Thatcher, N., Walling, J., Hansen, H.H., 1994. Single agent activity of weekly gemcitabine in advanced non-small cell lung cancer: a phase II study. J Clin Oncol, 12(9):1821-1826.

[4] Bhargava, P., Marshall, J.L., Fried, K., Williams, M., Lefebvre, P., Dahut, W., Hanfelt, J., Gehan, E., Figuera, M., Hawkins, M.J., Rizvi, N.A., 2001. Phase I and pharmacokinetic study of two sequences of gemcitabine and docetaxel administered weekly to patients with advanced cancer. Cancer Chemother Pharmacol, 48(2):95-103.

[5] Gandhi, V., Plunkett, W., 1990. Modulatory activity of 2′,2′-difluorodeoxycytidine on the phosphorylation and cytotoxicity of arabinosyl nucleosides. Cancer Res, 50(12):3675-3680.

[6] Green, M.R., 1996. Gemcitabine safety overview. Semin Oncol, 23(5 suppl 10):32-35.

[7] Grunewald, R., Kantarjian, H., Keating, M.J., Abbruzzese, J., Tarassoff, P., Plunkett, W., 1990. Pharmacologically directed design of the dose rate and schedule of 2′,2′-difluorodeoxycytidine (gemcitabine) administration in leukemia patients. Cancer Res, 50(21):6823-6826.

[8] Grunewald, R., Abbruzzese, J.L., Tarassoff, P., Plunkett, W., 1991. Saturation of 2′,2′-difluorodeoxycytidine 5′-triphosphate accumulation by mononuclear cells during a phase I trial of gemcitabine. Cancer Chemother Pharmacol, 27(4):258-262.

[9] Guchelaar, H.J., Richel, D.J., van Knapen, A., 1996. Clinical, toxicological and pharmacological aspects of gemcitabine. Cancer Treat Rev, 22(1):15-31.

[10] Huang, P., Chubb, S., Hertel, L.W., Grindey, G.B., Plunkett, W., 1991. Action of 2′,2′-difluorodeoxycytidine on DNA synthesis. Cancer Res, 51(22):6110-6117.

[11] Kroep, J.R., Giaccone, G., Voorn, D.A., Smit, E.F., Beijnen, J.H., Rosing, H., van Moorsel, C.J., van Groeningen, C.J., Postmus, P.E., Pinedo, H.M., Peters, G.J., 1999. Gemcitabine and paclitaxel: pharmacokinetic and pharmacodynamic interactions in patients with non-small-cell lung cancer. J Clin Oncol, 17(7):2190-2197.

[12] Lund, B., Ryberg, M., Petersen, P.M., Anderson, H., Thatcher, N., Dombernowsky, P., 1994. Phase II study of gemcitabine (2',2'-difluorodeoxycytidine) given as a twice weekly schedule to previously untreated patients with non-small cell lung cancer. Ann Oncol, 5(9):852-853.

[13] Manuel, D., Laura, G.E., Ana, L., 2002. A phase II trial of a two hour infusion of gemcitabine with carboplatin for advanced non-small-cell lung cancer (NSCLC). Ann Oncol, 13(suppl. 5):143.

[14] Ruiz van Haperen, V.W., Veerman, G., Vermorken, J.B., Peters, G.J., 1993. 2′,2′-difluorodeoxycytidine (gemcitabine) incorporation into RNA and DNA of tumor cell lines. Biochem Pharmacol, 46(4):762-766.

[15] Shord, S.S., Faucette, S.R., Gillenwater, H.H., Pascatore, S.L., Hawke, R.L., Socinski, M.A., Lindley, C., 2003. Gemcitabine pharmacokinetics and interaction with paclitaxel in patients with advanced non-small-cell lung cancer. Cancer Chemother pharmacol, 51(4):328-336.

[16] Storniolo, A.M., Allerheiligen, S.R., Pearce, H.L., 1997. Preclinical, pharmacologic, and phase I studies of gemcitabine. Semin Oncol, 24(2 Suppl 7):2-7.

[17] Tempero, M., Plunkett, W., Ruiz van Haperen, V., Hainsworth, J., Hochster, H., Lenzi, R., Abbruzzese, J., 2003. Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol, 21(18):3402-3408.