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.
Department of Medical Oncology, Hospital Arnau de Vilanova, Valencia, Spain. juan_osc@gva.es
Oscar
O
Juan
Amparo
A
Rocher
Agustín
A
Sánchez
José Javier
JJ
Sánchez
Vicente
V
Alberola
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