Pharmacokinetics of aprepitant and dexamethasone after administration of chemotherapeutic agents and effects of plasma substance P concentration on chemotherapy-induced nausea and vomiting in Japanese cancer patients.
OBJECTIVE
This study was conducted to determine the pharmacokinetics of aprepitant and dexamethasone as well as the relationship between the plasma concentration of substance P and nausea/vomiting in Japanese cancer patients.


METHODS
After administration of aprepitant (125/80 mg group [10 patients]: 125 mg on day 1 and 80 mg on days 2-5; 40/25 mg group [10 patients]: 40 mg on day 1 and 25 mg on days 2-5) and dexamethasone (6 mg on day 1 and 4 mg on days 2 and 3 in the 125/80 mg group, and 8 mg on day 1 and 6 mg on days 2 and 3 in the 40/25 mg group) to Japanese cancer patients receiving at least moderately emetogenic antitumor agents, the plasma concentrations of aprepitant, dexamethasone, and substance P were measured.


RESULTS
All of 20 patients were treated with the highly emetogenic agent cisplatin (≥70 mg/m(2)). The C(max) and AUC(0-24 h) of aprepitant in Japanese cancer patients were similar with those in non-Japanese patients. The clearance of dexamethasone in the 125/80 mg group was approximately one-half of that previously determined in the absence of aprepitant. The substance P concentration in plasma significantly increased only in patients with delayed nausea/vomiting.


CONCLUSIONS
This study demonstrated similar plasma pharmacokinetics of aprepitant in Japanese and non-Japanese, the validity of reducing dexamethasone dose, and the existence of increased plasma substance P concentration in patients receiving highly emetogenic cisplatin-based chemotherapy.
Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan. t.takahashi@scchr.jp
Toshiaki
T
Takahashi
Yukiko
Y
Nakamura
Asuka
A
Tsuya
Haruyasu
H
Murakami
Masahiro
M
Endo
Nobuyuki
N
Yamamoto
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000932:Antiemetics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D000077608:Aprepitant; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy; D003907:Dexamethasone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D017829:Granisetron / Q000627:therapeutic use; D006801:Humans; D007124:Immunoenzyme Techniques; D007564:Japan; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy; D008297:Male; D008654:Mesothelioma / Q000150:complications / Q000188:drug therapy; D008875:Middle Aged; D009025:Morpholines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced* / Q000188:drug therapy*; D055752:Small Cell Lung Carcinoma / Q000150:complications / Q000188:drug therapy; D013373:Substance P / Q000097:blood*; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy*; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D000932:Antiemetics; D000970:Antineoplastic Agents; D000077608:Aprepitant; D003907:Dexamethasone; D017829:Granisetron; D009025:Morpholines; D013373:Substance P