title: Effect of ceftriaxone and cefepime on high-dose methotrexate clearance.
abstract: Numerous drug interactions with methotrexate have been identified, which can lead to serious life-threatening effects. Up to 90% of methotrexate is excreted unchanged in the urine with primary excretion dependent on organic anion transport in the renal proximal tubule. The two pathways responsible for methotrexate secretion are organic anion transport 1 and primarily organic anion transport 3. Penicillins undergo tubular secretion via organic anion transport, and cephalosporins are believed to also possess a similar risk when administered with methotrexate; however, there are no human studies observing this interaction with cephalosporins and methotrexate. Ceftriaxone undergoes biliary clearance and has low affinity for the same organic anion transports as methotrexate; therefore, ceftriaxone has a low potential to interact with methotrexate. Cefepime is primarily secreted by organic cation transport N2, and also has a low potential to interact with methotrexate. This case report describes the pharmacokinetic effect of concomitant beta-lactam therapy in a patient receiving high-dose methotrexate.
authors.affiliation: Department of Pharmacy, Baylor University Medical Center, Baylor Scott & White Health, Dallas, Texas, USA.
authors.forename: Hieu X
authors.initials: HX
authors.lastname: Tran
authors.affiliation: Department of Pharmacy, Scott & White Memorial Hospital, Baylor Scott & White Health, Temple, Texas, USA Department of Medicine, Health Science Center, Texas A&M University, Temple, Texas, USA jherrington@sw.org.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Herrington
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy; D000077723:Cefepime; D002443:Ceftriaxone / Q000008:administration & dosage*; D002511:Cephalosporins / Q000008:administration & dosage*; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000097:blood* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000964:Antimetabolites, Antineoplastic; D002511:Cephalosporins; D002443:Ceftriaxone; D000077723:Cefepime; D008727:Methotrexate
keywords: Methotrexate; OAT; cefepime; ceftriaxone; drug interactions; organic anion transport; pharmacokinetics