Antipyrine test predicts pharmacodynamics in docetaxel and cisplatin combination chemotherapy.
To clarify the role 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 24h after oral administration of 500 mg antipyrine. Antipyrine disappearance rate (ADR) was calculated by: [(C(4h)-C(24h))/C(4h)]x100. ADR 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 role in predicting toxicities of docetaxel and cisplatin combination chemotherapy.
Nishio
Makoto
M
Division of Internal Medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Kami-ikebukuro 1-37-1, Toshima-ku, Tokyo 170-8455, Japan. mnishio@jfcr.or.jp
Matsuda
Masanori
M
Ohyanagi
Fumiyoshi
F
Sato
Yukitohi
Y
Okumura
Sakae
S
Tabata
Daisuke
D
Morikawa
Akinobu
A
Nakagawa
Ken
K
Horai
Takeshi
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000983:Antipyrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000556:secondary; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018450:Disease Progression; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D043823:Taxoids; D000077143:Docetaxel; D003577:Cytochrome P-450 Enzyme System; D002945:Cisplatin; D000983:Antipyrine