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

Our plain-English summary of 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, by T. Takahashi, Y. Nakamura, A. Tsuya, et al (Cancer Chemotherapy and Pharmacology, 2011).

The study

• Authors: T. Takahashi, Y. Nakamura, A. Tsuya, H. Murakami, M. Endo, N. Yamamoto
• Journal: Cancer Chemotherapy and Pharmacology
• Published: 2011;68(3):653-9
• Type of article: Randomized trial
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This study concerns anti-nausea drugs during chemotherapy, not asbestos. Asbestos is not discussed; one of the 20 patients had mesothelioma (type not stated). In an open-label study, 20 Japanese cancer patients on cisplatin-based chemotherapy were randomized to one of two doses of the anti-nausea drug aprepitant, plus reduced-dose dexamethasone, a steroid. Blood levels of both drugs and of substance P, a body chemical linked to vomiting, were measured. For the 125 mg aprepitant dose, versus non-Japanese patients in an earlier study, geometric mean ratios were 1.09 (90% confidence interval 0.79 to 1.52) for peak level and 1.12 (0.87 to 1.45) for 24-hour exposure. In the higher-dose group, dexamethasone clearance was 6.48 litres per hour, roughly 52% below the 13.3 reported earlier for Japanese patients without aprepitant. Substance P rose significantly on days 2 to 4. Among 19 patients with complete baseline data, the rise was statistically significant only in those with delayed nausea or vomiting. The authors concluded that aprepitant behaved similarly in Japanese and non-Japanese patients and that reducing the dexamethasone dose was valid.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Open-label randomized pharmacokinetic study comparing two aprepitant dose regimens
• Who was studied: 20 Japanese cancer patients aged 20 to 74 receiving chemotherapy: 18 with non-small cell lung cancer, 1 with small-cell lung cancer and 1 with mesothelioma (site not stated). All received cisplatin at 70 mg/m2 or more. Ten patients were in each dose group. Study dates are not given. The authors are at Shizuoka Cancer Center, Japan.
• Exposure: No asbestos exposure was studied. The study examined the anti-nausea drug aprepitant, given orally either as 125 mg on day 1 and 80 mg on days 2 to 5, or as 40 mg on day 1 and 25 mg on days 2 to 5. It was given with intravenous dexamethasone: 6 mg then 4 mg in the higher-dose group, and 8 mg then 6 mg in the lower-dose group.
• Main results:
  • At the 125 mg aprepitant dose, Japanese patients were compared with non-Japanese cancer patients from an earlier study. The geometric mean ratio for aprepitant peak concentration was 1.09 (90% CI 0.79 to 1.52). For 24-hour exposure it was 1.12 (90% CI 0.87 to 1.45).
  • In the 125/80 mg group, aprepitant 24-hour exposure on days 1 and 5 rose more than in proportion to the dose, compared with the 40/25 mg group.
  • Dexamethasone clearance was 6.48 L/h in the 125/80 mg group and 10.0 L/h in the 40/25 mg group. Earlier work in Japanese patients without aprepitant reported 13.3 L/h. The authors described these as decreases of approximately 52% and 25%.
  • Across all 20 patients, plasma substance P rose significantly on days 2 to 4 compared with day 1.
  • Among the 19 patients with day-1 data, substance P rose significantly between days 2 and 5 in patients with delayed nausea or vomiting. In patients without delayed nausea or vomiting, the increase was not statistically significant. The number of patients in each subgroup is not given.
• The authors' conclusion: The authors concluded that aprepitant pharmacokinetics were similar in Japanese and non-Japanese patients and that reducing the dexamethasone dose was valid. They also concluded that substance P concentration increased in patients receiving highly emetogenic chemotherapy.
• Limitations the authors state:
  • Substance P levels in this study (2 to 55 pg/mL) were much lower than in another report (0 to 1,608 pg/mL). The authors said the cause was unknown but may relate to the different assay kits used.

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Cisplatin.

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