The NK1 receptor antagonist aprepitant does not alter the pharmacokinetics of high-dose melphalan chemotherapy in patients with multiple myeloma
What is already known about this subject: Nausea and vomiting are the most distressing side-effects of a high dose melphalan regimen. Aprepitant in addition to an antiemetic standard regimen has been reported to improve significantly both acute and delayed chemotherapy-induced nausea and vomiting. -...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
30 August 2010
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| In: |
British journal of clinical pharmacology
Year: 2010, Volume: 70, Issue: 6, Pages: 903-907 |
| ISSN: | 1365-2125 |
| DOI: | 10.1111/j.1365-2125.2010.03792.x |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1365-2125.2010.03792.x Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2125.2010.03792.x 
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| Author Notes: | Gerlinde Egerer, Kathrin Eisenlohr, Martina Gronkowski, Juergen Burhenne, Klaus-Dieter Riedel & Gerd Mikus |
| Summary: | What is already known about this subject: Nausea and vomiting are the most distressing side-effects of a high dose melphalan regimen. Aprepitant in addition to an antiemetic standard regimen has been reported to improve significantly both acute and delayed chemotherapy-induced nausea and vomiting. - What this study adds: Anti-emetic regimens including aprepitant have no clinically relevant effect on the pharmacokinetics of the anticancer agent melphalan when administered 1 h before high dose melphalan infusion. - Aims: The objective of this investigation was to assess the effect of aprepitant on the pharmacokinetics of high-dose melphalan used as conditioning therapy before blood stem cell transplantation in multiple myeloma. - Methods: Aprepitant (125 mg) or placebo was administered 1 h before melphalan therapy (1 h infusion of 100 mg m−2). Eleven plasma samples were obtained over 8 h and melphalan was quantified using an LC/MS/MS method. Standard pharmacokinetic parameters were calculated and nonparametric testing was applied to assess the differences between aprepitant and placebo treatment. - Results: Twenty patients received placebo and 10 patients aprepitant treatment. There were no differences observed for Cmax at the end of melphalan infusion (placebo 3431 ± 608 ng ml−1vs. aprepitant 3269 ± 660 ng ml−1). In addition, AUC and terminal elimination half-life were not changed by aprepitant. Total clearance of melphalan was 304 ± 58 ml min−1 m−2 (placebo) which was not influenced by aprepitant (288 ± 78 ml min−1 m−2). - Conclusions: The administration of the NK1 receptor antagonist aprepitant 1 h before a high-dose chemotherapy does not influence the exposure and the elimination of melphalan. Therefore, oral administration of 125 mg aprepitant 1 h before melphalan infusion does not alter the disposition of intravenously administered melphalan. |
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| Item Description: | Im Titel ist die Ziffer 1 bei "NK1" tiefgestellt Gesehen am 02.03.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1365-2125 |
| DOI: | 10.1111/j.1365-2125.2010.03792.x |