Pharmacokinetically-guided dosing of pemetrexed in a patient with renal impairment and a patient requiring hemodialysis. (April 2019)

• Record Type: Journal Article
• Authors: de Rouw, N.; Croes, S.; Posthuma, R.; Agterhuis, D.E.; Schoenmaekers, J.J.A.O.; Derijks, H.J; Burger, D.M.; Dingemans, A.M.; ter Heine, R.
• Is Part Of: Lung cancer. Volume 130(2019)
• Page Start: 156
• Page End: 158
• Publication Date: 2019-04
• Subjects: Pemetrexed -- Non-small cell lung cancer -- Renal impairment -- Pharmacokinetics; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.01.018
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Renal impairment is highly prevalent in lung cancer patients. Pemetrexed is currently contraindicated in patients with creatinine clearance <45 mL/min. Pharmacokinetically-guided dosing of pemetrexed seems a feasible treatment strategy for these patients. Abstract: Objectives: Pemetrexed is indicated for non-small cell lung cancer and mesothelioma. Dosing is based on body surface are (BSA), while renal function is the only determinant for exposure and thus toxicity. BSA-based dosing introduces large variability in exposure and may lead to (hemato)toxicity in patients with impaired renal function. Therefore, pemetrexed is contraindicated in renal impairment. The presented cases provide proof-of-concept for pharmacokinetically-guided dosing of pemetrexed in a haemodialysis patient and a patient with mild renal impairment. Methods: The pharmacokinetic target was an area under the concentration-time curve (AUC) of 123–205 mg·h/L. Using a previously developed population pharmacokinetic model, individual pharmacokinetics were estimated. Results: Both patients had an exposure above target after the initial dose, but a proportional dose reduction resulted in a therapeutic exposure in both patients (185 and 166 mg·h/L, respectively), that was well-tolerated. Interestingly, a threefold increase in systemic clearance of pemetrexed was observed during hemodialysis (from 1.00 L/h to 3.01 L/h), which approximates the population clearance of pemetrexed. Conclusion: Altogether, we showed that pharmacokinetically-guided dosing of pemetrexed may be a feasible strategy for patients with lung cancer and renal impairment.