Pharmacokinetic study of paclitaxel as a 3-hour infusion in an Indian population: 135 mg/m2 vs. 175 mg/m2.
The objective of this clinical study was to determine the pharmacokinetic parameters of paclitaxel at doses of 135 and 175 mg/m2 when given as a 3-hour infusion in an Indian population. Twelve cancer patients of both sexes participated in the study and a parallel experimental design was adopted for the assignment of doses to patients. A solid phase extraction technique was used for sample clean-up followed by a reversed phase HPLC assay for the analysis of paclitaxel in plasma samples. Pharmacokinetic parameters such as Cmax, AUC0-infinity, T1/2 beta, AUMC0-infinity, VSS, VZ and CLT were determined by a compartment model-independent method using a PCNONLIN package. Teff and AUCeff were also calculated and compared at the two doses by considering a plasma concentration of > or = 0.05 microM as threshold. The mean Cmax and AUC0-infinity values were 2.57 microM and 12.06 microM at the 135 mg/m2 dose level while at the 175 mg/m2 dose the values increased to 4.96 microM and 9.52 microM.h/l, respectively. It was found that the 135 mg/m2 dose resulted in greater mean CLT and VSS values than the 175 mg/m2 dose. The disposition of paclitaxel was found to be nonlinear and the pertinent pharmacokinetic parameters were comparable to those from previous clinical studies. It was concluded from the present study that further clinical trials of paclitaxel alone or in combination with other drugs should be undertaken cautiously, taking into consideration its nonlinear pharmacokinetics which necessitate proper adjustment of the infusion schedule and/or dose to avoid any adverse consequences to the patient.
Dhanikula
A B
AB
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research.
Panchagnula
R
R
Singh
I
I
Kaur
K J
KJ
Kaul
C L
CL
Sekhon
J S
JS
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007194:India; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D017239:Paclitaxel / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel