Quantitative effect of gender, age, liver function, and body size on the population pharmacokinetics of paclitaxel in patients with solid tumors

Markus Joerger, Alwin D.R. Huitema, Desiree H.J.G. Van Den Bongard, Jan H.M. Schellens, Jos H. Beijnen

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100 Citaten (Scopus)

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Background: The aim of this study was to quantitatively assess the effect of anthropometric and biochemical variables and third-space effusions on paclitaxel pharmacokinetics in solid tumor patients. Materials and Methods: Plasma concentration-time data of paclitaxel were collected in patients with non - small cell lung cancer (n = 84), ovarian cancer (n = 40), and various solid tumors (n = 44), totaling 168 patients. Paclitaxel was given as a 3-hour infusion (n = 163) at doses ranging from 100 to 250 mg/m2, or as a 24-hour infusion (n = 5) at a dose of 135 or 175 mg/m2. Data were analyzed using nonlinear mixed-effect modeling. Results: A three-compartment model with saturable elimination and distribution was used to describe concentration-time data. Male gender and body surface area were positively correlated with maximal elimination capacity of paclitaxel (VMEL); patient age and total bilirubin were negatively correlated with VMEL (P < 0.005 for all correlations). Typically, male patients had a 20% higher VMEL; a 0.2 m2 increase of body surface area led to a 9% increase of VMEL; a 10-year increase of patient age led to a 5% decrease of VMEL; and a 10-μmol increase of total bilirubin led to a 14% decrease of VMEL. Third-space effusions were not correlated with paclitaxel pharmacokinetics. Conclusions: This extended retrospective population analysis showed patient gender to significantly and independently affect paclitaxel distribution and elimination. Body surface area, total bilirubin, and patient age were confirmed to affect paclitaxel elimination. This pharmacokinetic model allowed quantification of the covariate effects on the elimination of paclitaxel and may be used for covariate-adapted paclitaxel dosing.

Originele taal-2Engels
Pagina's (van-tot)2150-2157
Aantal pagina's8
TijdschriftClinical Cancer Research
Volume12
Nummer van het tijdschrift7 I
DOI's
StatusGepubliceerd - 1 apr. 2006
Extern gepubliceerdJa

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