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The influence of ageing on cisplatin pharmacokinetics in lung cancer patients with normal organ function
Authors:Nobuyuki Yamamoto  Tomohide Tamura  Mitsuaki Maeda  Masasi Ando  Tetsu Shinkai  Kenji Eguchi  Yuichiro Ohe  Fumihiro Oshita  Jun-ichi Shiraishi  Noriyuki Katsumata  Nagahiro Saijo
Affiliation:(1) Department of Medical Oncology, National Cancer Center Hospital, 1-1, Tsukiji 5-chome, Chuo-ku, 104 Tokyo, Japan;(2) Chemotherapy and Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, 104 Tokyo, Japan;(3) Pharmacology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, 104 Tokyo, Japan
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.
Keywords:Cisplatin  Ageing  Pharmacokinetics
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