Abstract
This study was performed to identify any relationship between age and cisplatin (CDDP) pharmacokinetics in lung cancer patients. CDDP was given at a dose of 80 mg/m2 by 1-h intravenous infusion to 23 lung cancer patients. All patients had normal renal, hepatic, and bone marrow functions. We measured ultrafilterable platinum (U-Pt) and total plasma platinum (T-Pt) using atomic absorption spectrometry. There was significant correlation between the age of the patients and U-Pt pharmacokinetic parameters such as the area under the plasma concentration versus time curve (AUC), total clearance (Cl), and peak plasma concentration (Cmax) as well as the AUC of T-Pt (P<0.05). We performed univariate regression analysis to examine the influence of factors aside from age on the AUC of U-Pt and T-Pt. Creatinine and GPT levels were significantly related to the AUC of U-Pt, and creatinine clearance and creatinine concentrations were significantly related to the AUC of T-Pt. Therefore, stepwise multiple-regression models for the AUC of U-Pt and T-Pt were developed to assess an age effect. Age was consistently an independent and significant predictor of the AUC of U-Pt and T-Pt.
Similar content being viewed by others
References
Borkowski JM, Duerr M, Donehower RC, Rowinsky EK, Chen TL, Ettinger DS, Grochow LB (1994) Relation between age and the clearance rate of nine investigational anticancer drugs from phase I pharmacokinetic data. Cancer Chemother Pharmacol 33:493
Bunn PA (1989) The expanding role of cisplatin in the treatment of non-small-cell lung cancer. Semin Oncol 16:10
Greenblatt DJ, Koch-Water J (1975) Drug therapy: clinical pharmacokinetics. N Engl J Med 293:702
Miya T, Sasaki Y, Karato A, Saijo N (1992) Pharmacokinetic study of mitomycin C with emphasis on the influence of ageing. Jpn J Cancer Res 83:1382
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFradden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649
Powis G (1985) Anticancer drug pharmacodynamics. Cancer Chemother Pharmacol 14:177
Reece PA, Stafford I, Russel J, Khan M, Gill PG (1987) Creatinine clearance as a predictor of ultrafilterable platinum disposition in cancer patients treated with cisplatin: relationship between peak ultrafiltreable platinum plasma levels and nephrotoxicity. J Clin Oncol 5:304
Schmucker DL (1985) Ageing and drug disposition: an update. Pharmacol Rev 37:133–148
Tregaskins BF, Stevenson IH (1990) Pharmacokinetics in old age. Br Med Bull 46:9
Weiner MW, Jacobs C (1983) Mechanism of cisplatin nephrotoxicity. Fed Proc 42:2974
Yamaoka K, Nakagawa T, Uno T (1978) Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 6:165
Yamaoka K, Tanigawara Y, Nakagawa T, Uno T (1981) A pharmacokinetic analysis program (MULTI) for microcomputers. J Pharmacobiodyn 4:879
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yamamoto, N., Tamura, T., Maeda, M. et al. The influence of ageing on cisplatin pharmacokinetics in lung cancer patients with normal organ function. Cancer Chemother. Pharmacol. 36, 102–106 (1995). https://doi.org/10.1007/BF00689192
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00689192