INDIVIDUAL DIFFERENCES OF TAXOL PHARMACOKINETICS IN BREAST CANCER PATIENTS

Objective: Analysis of pharmacokinetic parameters of Taxol® (paclitaxel) in patients with breast cancer in repeated infusions and determination of possible individual differences



Methods: Paclitaxel plasma concentrations were determined by HPLC with UV detection in 8 breast cancer patients before, during 60min of infusion and 10 to 1 380 min after infusion.

Results: Pharmacokinetic parameters of the individual patients did not significantly change during 3 repeated weekly infusions. However, these parameters (half-lives t0,5α, t 0.5β and 0.5γ and corresponding rates, intercepts, area under concentration AUC0-t, AUC0-∞, mean residence time, volume at the steady state, maximal concentration and clearance) were significantly different among the patients as proved by parametric analysis ANOVA. Significant differences among the patients detected by the Barttlett’s test for variability were confirmed by the non-parametric Kruskal-Wallis test. The individual values of t0.5α of all patients significantly correlated with t0.5β (r = 0.587, p < 0.01), but there was no correlation between t0.5β and t0.5γ. The observed differences between patients with most rapid and slowest elimination of paclitaxel were 3.2-fold (AUC0-t), 3.6-fold (CL0-t and CL0-∞) and 3-fold (CL/kg). In accordance, the difference in rate of α phase in these patients was 3-fold and t0.5α was also shorter in the patient with the most rapid clearance. Similar differences were found in β phase. Moreover, the patient with the lowest clearance had 2.4-higher maximal concentration (Cmax).

Conclusion: Pharmacokinetic parameters in the followed patients were significantly different and the differences remained unchanged during repeated infusions. These differences could potentially influence outcome of the therapy.

Keywords: Taxol®, paclitaxel, pharmacokinetics, breast cancer, individual differences