RESUMEN

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 C(max) at the end of melphalan infusion (placebo 3431 ± 608 ng ml⁻¹ vs. 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.

Asunto(s)

Antieméticos/farmacología , Antineoplásicos Alquilantes/sangre , Melfalán/sangre , Morfolinas/farmacología , Mieloma Múltiple/sangre , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Aprepitant , Método Doble Ciego , Esquema de Medicación , Interacciones Farmacológicas , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Infusiones Intravenosas , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Antagonistas del Receptor de Neuroquinina-1 , Estudios Prospectivos , Acondicionamiento Pretrasplante/métodos