title: A case of melphalan sustained accumulation in an 80-year old patient.
abstract: Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.
authors.affiliation: Service de Pharmacie, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, 75012, Paris, France. pierrealain.jolivot@aphp.fr.|Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), 75012, Paris, France. pierrealain.jolivot@aphp.fr.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Jolivot
authors.affiliation: Gustave Roussy Cancer Campus - Service interdépartemental de Pharmacologie et d'Analyse du Médicament (SIPAM), 94800, Villejuif, France.
authors.forename: Vianney
authors.initials: V
authors.lastname: Poinsignon
authors.affiliation: Gustave Roussy Cancer Campus - Service interdépartemental de Pharmacologie et d'Analyse du Médicament (SIPAM), 94800, Villejuif, France.
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), 75012, Paris, France.|Service de Réanimation médicale, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, 75012, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guidet
authors.affiliation: Service de Réanimation médicale, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, 75012, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Pichereau
authors.affiliation: Service de Pharmacie, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, 75012, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), 75012, Paris, France.|Faculté de Pharmacie, Université Paris-Sud, 92290, Chatenay-Malabry, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Fernandez
authors.affiliation: Service de Pharmacie, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, 75012, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), 75012, Paris, France.|Faculté de Pharmacie, Université Paris-Sud, 92290, Chatenay-Malabry, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hindlet
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000628:therapy; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000493:pharmacokinetics; D003422:Critical Care; D004347:Drug Interactions; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications; D008558:Melphalan / Q000009:adverse effects* / Q000493:pharmacokinetics; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000188:drug therapy; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects
chemical_list: D000890:Anti-Infective Agents; D018906:Antineoplastic Agents, Alkylating; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D008558:Melphalan
keywords: Acute kidney injury; Drug interactions; Melphalan; Multiple myeloma; Pancytopenia; Trimethoprim–sulfamethoxazole combination