Antipyrine test predicts pharmacodynamics in docetaxel and cisplatin combination chemotherapy

To clarify the rote of cytochrome P450 in docetaxel and cisplatin combination chemotherapy, cytochrome P450 activity was measured by simple antipyrine test, and its correlation with the drugs' pharmacodynamics was assessed. Twenty-five patients with advanced non-small cell lung cancer received an antipyrine test and were treated with docetaxel and cisplatin. Plasma antipyrine concentration (C) was measured 4 and 24 h after oral administration of 500 mg antipyrine. Antipyrine disappearance rate (ADR) was calculated by: [(C-4h - C-24h)/C-4h] x 100. ADIR correlated significantly with neutropenia nadir. ADR and alpha(1)-acid glycoprotein were selected for independent predictors of neutropenia by multiple regression analysis. In addition, 25 patients were separated into "low ADR" (<40%) and "high ADR" groups (>40%). Grade 3-4 neutropenia was observed in 7/9 "low ADR-patients (77%), whereas grade 3-4 neutropenia was observed in 5/16 "high ADR-patients (31%). We concluded that antipyrine test and cytochrome P450 play an important rote in predicting toxicities of docetaxel and cisplatin combination chemotherapy. (C) 2005 Elsevier Ireland Ltd. All rights reserved.