Influence of the cyto-protective agent amifostine on the pharmacokinetics of low-dose Paclitaxel.
BACKGROUND
Pharmacokinetic parameters (PHK) of low-dose weekly paclitaxel (PAC) are not well known, particularly when administered with the cytoprotective agent amifostine (AMI).


METHODS
Patients with non-small cell lung cancer (NSCLC) received PAC alone or PAC + AMI. Blood samples were drawn at the end of the infusion at 0, 0.25, 0.5, 1, 2 and 4 h for the measurement of plasma PAC using HPLC. Area under the concentration-time curve (AUC), the peak plasma concentrations (Cmax) and the residence time of paclitaxel in plasma at concentrations >0.1 microM (TPP >or=0.1) and >0.05 microM (TPP >or=0.05) were calculated using a two-compartmental model. ANOVA was used for statistical analysis.


RESULTS
Pharmacokinetic studies were completed for 43 doses among 11 patients receiving PAC alone and for 26 doses among 8 patients receiving the combination AMI + PAC (from the first to the fifth week). Statistically significant differences in all parameters except AUC were observed between the 2 treatment groups. A significantly higher Cmax was observed for patients receiving PAC + AMI versus PAC alone. Both TPP >or=0.1 and TPP >or=0.05 were also more prolonged in AMI + PAC cycles.


CONCLUSIONS
AMI produces a prolongation in PAC plasma circulation time. Further specifically designed studies are needed to quantify the resultant effects on PAC's efficacy and toxicity.
Juan
Oscar
O
Department of Medical Oncology, Hospital Arnau de Vilanova, Valencia, Spain. juan_osc@gva.es
Rocher
Amparo
A
Sánchez
Agustín
A
Sánchez
José Javier
JJ
Alberola
Vicente
V
D004999:Amifostine / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D011837:Radiation-Protective Agents; D004999:Amifostine; D017239:Paclitaxel