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

PURPOSE: 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.