[Proposal of a novel dosing schedule of docetaxel by using alpha1-acid glycoprotein as an index].
This study was aimed to propose a novel dosing schedule of docetaxel based on alpha(1)-acid glycoprotein (AGP)as an index. For this purpose, we performed Monte Carlo simulation using a population pharmacokinetic/pharmacodynamic (PPK/PPD) model, which we previously developed to estimate the ANC Nadir distribution after docetaxel administration. AGP values, which were incorporated in PPK/PPD, were sampled from normal distributions (S.D. 44, range from 19 to 259), as various mean levels of 125, 150, 175 and 200 (mg/dl). Monte Carlo simulation was conducted using docetaxel doses of 40, 50 and 60 (mg/m(2)) for each AGP distribution. Simulation was performed 200 times, and distributions of ANC Nadir median were obtained from simulations. We accepted a dose when 20 percentile of the distribution of ANC Nadir median was greater than 500 (counts/microl), in order to avoid the grade 4 neutropenia. From the results of simulations, 40, 50, 60 and 60 doses (mg/m(2)) were recommended for 125, 150, 175, and 200 AGP mean (mg/dl) respectively. Secondly, to evaluate this dosing schedule, we adopted these recommended doses to 16 patients whose ANC Nadir observed is lesser than 500, and simulated the ANC Nadir. The number of patients whose simulated time below ANC=500 was higher than 6 days decreased from 8 to 2, implying that this dosing schedule might be effective to avoid neutropenia induced by docetaxel. In conclusion, we proposed a novel dosing schedule of docetaxel using AGP as an index, which might be effective to avoid neutropenia induced by docetaxel.
Ozawa
Kazuhiro
K
Department of Clinical and Molecular Pharmacokinetics/Pharmacodynamics, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan. kazuoza@pharm.showa-u.ac.jp
Minami
Hironobu
H
Sato
Hitoshi
H
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D006801:Humans; D008954:Models, Biological; D009010:Monte Carlo Method; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D009961:Orosomucoid; D012015:Reference Standards; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D009961:Orosomucoid; D043823:Taxoids; D000077143:Docetaxel