PURPOSE:Pemetrexed is an antimetabolite that is structurally similar to methotrexate. Because nonsteroidal anti-inflammatory drugs (NSAID) impair methotrexate clearance and increase its toxicity, we evaluated the pharmacokinetics and toxicity of pemetrexed when coadministered with aspirin or ibuprofen in advanced cancer patients. EXPERIMENTAL DESIGN: In two independent, randomized, crossover drug interaction studies, cancer patients with a creatinine clearance (CrCl) > or =60 mL/min received anNSAID (aspirin or ibuprofen) with either the first or the second dose of pemetrexed (cycle 1 or 2). Pemetrexed (500 mg/m(2)) was infused i.v. on day 1 of a 21-day cycle, and all patients were supplemented with oral folic acid and i.m. vitamin B(12). Aspirin (325 mg) or ibuprofen (400 mg; 2 x 200 mg) was given orally every 6 hours, starting 2 days before pemetrexed administration, with the ninth and final dose taken 1 hour before infusion. Pemetrexed pharmacokinetics with and without concomitant NSAID treatment were compared for cycles 1 and 2. RESULTS: Data from 27 patients in each study were evaluable for the analysis of pemetrexed pharmacokinetics. Coadministration of aspirin did not alter pemetrexed pharmacokinetics; however, ibuprofen coadministration was associated with a 16% reduction in clearance, a 15% increase in maximum plasma concentration, and a 20% increase in area under the plasma concentration versus time curve but no significant change in V(ss) compared with pemetrexed alone. No febrile neutropenia occurred in any patient, and no increase in pemetrexed-related toxicity was associated with NSAID administration. CONCLUSIONS:Pemetrexed (500 mg/m(2)) with vitamin supplementation is well tolerated and requires no dosage adjustment when coadministered with aspirin (in patients with CrCl > or =60 mL/min) or ibuprofen (in patients with CrCl > or =80 mL/min).
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PURPOSE:Pemetrexed is an antimetabolite that is structurally similar to methotrexate. Because nonsteroidal anti-inflammatory drugs (NSAID) impair methotrexate clearance and increase its toxicity, we evaluated the pharmacokinetics and toxicity of pemetrexed when coadministered with aspirin or ibuprofen in advanced cancerpatients. EXPERIMENTAL DESIGN: In two independent, randomized, crossover drug interaction studies, cancerpatients with a creatinine clearance (CrCl) > or =60 mL/min received an NSAID (aspirin or ibuprofen) with either the first or the second dose of pemetrexed (cycle 1 or 2). Pemetrexed (500 mg/m(2)) was infused i.v. on day 1 of a 21-day cycle, and all patients were supplemented with oral folic acid and i.m. vitamin B(12). Aspirin (325 mg) or ibuprofen (400 mg; 2 x 200 mg) was given orally every 6 hours, starting 2 days before pemetrexed administration, with the ninth and final dose taken 1 hour before infusion. Pemetrexed pharmacokinetics with and without concomitant NSAID treatment were compared for cycles 1 and 2. RESULTS: Data from 27 patients in each study were evaluable for the analysis of pemetrexed pharmacokinetics. Coadministration of aspirin did not alter pemetrexed pharmacokinetics; however, ibuprofen coadministration was associated with a 16% reduction in clearance, a 15% increase in maximum plasma concentration, and a 20% increase in area under the plasma concentration versus time curve but no significant change in V(ss) compared with pemetrexed alone. No febrile neutropenia occurred in any patient, and no increase in pemetrexed-related toxicity was associated with NSAID administration. CONCLUSIONS:Pemetrexed (500 mg/m(2)) with vitamin supplementation is well tolerated and requires no dosage adjustment when coadministered with aspirin (in patients with CrCl > or =60 mL/min) or ibuprofen (in patients with CrCl > or =80 mL/min).
Authors: Andrea R Hagemann; Akiva P Novetsky; Israel Zighelboim; Feng Gao; L Stewart Massad; Premal H Thaker; Matthew A Powell; David G Mutch; Jason D Wright Journal: Gynecol Oncol Date: 2013-10-04 Impact factor: 5.482
Authors: Priya Kumthekar; Sean A Grimm; Michael J Avram; Virginia Kaklamani; Irene Helenowski; Alfred Rademaker; Mary Cianfrocca; William Gradishar; Jyoti Patel; Mary Mulcahy; Katie McCarthy; Jeffrey J Raizer Journal: J Neurooncol Date: 2013-01-25 Impact factor: 4.130
Authors: Daniel Scotcher; Christopher Jones; Maria Posada; Aleksandra Galetin; Amin Rostami-Hodjegan Journal: AAPS J Date: 2016-08-09 Impact factor: 4.009
Authors: Mario Occhipinti; Marta Brambilla; Giulia Galli; Sara Manglaviti; Maristella Giammaruco; Arsela Prelaj; Roberto Ferrara; Alessandro De Toma; Claudia Proto; Teresa Beninato; Emma Zattarin; Giuseppe Lo Russo; Alain Jonathan Gelibter; Maurizio Simmaco; Robert Preissner; Marina Chiara Garassino; Filippo De Braud; Paolo Marchetti Journal: J Pers Med Date: 2021-05-18