当前位置： SCI文献检索 > CANCER CHEMOTHERAPY AND PHARMACOLOGY期刊下所有文献 > Population pharmacokinetics of pemetrexed disodium (ALIMTA) in patients with cancer.

Population pharmacokinetics of pemetrexed disodium (ALIMTA) in patients with cancer.

Abstract：

PURPOSE:To evaluate the population pharmacokinetics of pemetrexed disodium in cancer patients enrolled in four different open-label, multicenter, nonrandomized phase II studies. METHODS:Pemetrexed disodium was administered as a 10-min intravenous infusion (600 mg/m2) every 21 days. A total of four blood samples were to be collected each cycle per patient (n= 103 patients) during cycles 1 and 3. Plasma concentration-time data were analyzed by nonlinear mixed-effect modeling using NONMEM to estimate pemetrexed disodium pharmacokinetic parameters (mean, and between- and within-patient variability) as well as relationships between the pharmacokinetic parameters and various patient-specific factors (demographic and physiologic data). RESULTS/CONCLUSIONS:The pharmacokinetics of pemetrexed disodium were best characterized by a two-compartment model with initial distribution and terminal elimination half-lives of 0.63 h and 2.73 h, respectively. The typical value of systemic clearance (CL) in liters per hour included a relationship to creatinine clearance (CrCL) with a slope of 0.0292. Typical values of central volume (V(c)), distributional CL (Q), and peripheral volume (V(p)) were 11.3 1, 3.21 l/h, and 5.20 l, respectively. Between-patient variability was 19.6%, 15.6%, and 21.7% for CL, V(c), and V(p), respectively. A combined additive/proportional error model was used to describe residual variability, with a coefficient of variation of 23.7% for the proportional component and a standard deviation of 0.0410 microg/ml for the additive component. Significant patient-specific factors on CL were calculated CrCL, body weight, and to a lesser extent alanine transaminase and folate deficiency. Gender and body weight were significant factors on V(c) while both body surface area and albumin were significant factors on V(p). In conclusion, population pharmacokinetic modeling revealed relationships between pharmacokinetic parameters and various patient specific factors.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Ouellet D,Periclou AP,Johnson RD,Woodworth JR,Lalonde RL

doi

10.1007/s002800000144

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

227-34

issue

eissn

0344-5704

issn

1432-0843

journal_volume

pub_type

杂志文章

在线工具

Population pharmacokinetics of pemetrexed disodium (ALIMTA) in patients with cancer.