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Sökning: onr:"swepub:oai:DiVA.org:uu-450118" > Rethinking the Appl...

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FältnamnIndikatorerMetadata
00004733naa a2200421 4500
001oai:DiVA.org:uu-450118
003SwePub
008210811s2021 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4501182 URI
0247 a https://doi.org/10.1007/s40262-020-00972-12 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a de Rouw, Nikkiu Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands.;Jeroen Bosch Hosp, Dept Pharm, Shertogenbosch, Netherlands.4 aut
2451 0a Rethinking the Application of Pemetrexed for Patients with Renal Impairment :b A Pharmacokinetic Analysis
264 c 2021-01-09
264 1b ADIS INT LTD,c 2021
338 a electronic2 rdacarrier
520 a Background Pemetrexed is used for the treatment for non-small cell lung cancer and mesothelioma. Patients with renal impairment are withheld treatment with this drug as it is unknown what dose is well tolerated in this population. Objective The purpose of our study was to investigate the pharmacokinetics (PK) of pemetrexed in patients with renal impairment. Methods A population PK analysis of pemetrexed was performed using non-linear mixed-effects modelling with phase I data obtained from the manufacturer. Additionally, the impact of renal function on pemetrexed PK was assessed with a simulation study using the developed PK model and a previously developed PK model lacking the phase I data. Results The dataset included 548 paired observations of 47 patients, with a wide range of estimated glomerular filtration rates (eGFR; 14.4-145.6 mL/min). Pemetrexed PK were best described by a three-compartment model with eGFR (calculated using the Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI] formula) as a linear covariate on renal pemetrexed clearance. Using the developed model, we found that renal clearance accounts for up to 84% (95% confidence interval 69-98%) of total pemetrexed clearance, whereas the manufacturer previously reported a 50% contribution of renal clearance. Conclusion Renal function is more important for the clearance of pemetrexed than previously thought and this should be taken into account in patients with renal impairment. Furthermore, a third compartment may contribute to prolonged exposure to pemetrexed during drug washout.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Urologi och njurmedicin0 (SwePub)302142 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Urology and Nephrology0 (SwePub)302142 hsv//eng
7001 a Boosman, Rene J.u Netherlands Canc Inst, Dept Pharm & Pharmacol, Amsterdam, Netherlands.4 aut
7001 a Huitema, Alwin D. R.u Netherlands Canc Inst, Dept Pharm & Pharmacol, Amsterdam, Netherlands.;Univ Utrecht, Med Ctr, Dept Clin Pharm, Utrecht, Netherlands.4 aut
7001 a Hilbrands, Luuk B.u Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, Nijmegen, Netherlands.4 aut
7001 a Svensson, Elin,d 1985-u Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands.4 aut0 (Swepub:uu)elisv718
7001 a Derijks, Hieronymus J.u Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands.;Jeroen Bosch Hosp, Dept Pharm, Shertogenbosch, Netherlands.4 aut
7001 a van den Heuvel, Michel M.u Radboud Univ Nijmegen, Med Ctr, Dept Pulm Dis, Nijmegen, Netherlands.4 aut
7001 a Burger, David M.u Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands.4 aut
7001 a ter Heine, Robu Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands.4 aut
7102 a Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands.;Jeroen Bosch Hosp, Dept Pharm, Shertogenbosch, Netherlands.b Netherlands Canc Inst, Dept Pharm & Pharmacol, Amsterdam, Netherlands.4 org
7730 t Clinical Pharmacokineticsd : ADIS INT LTDg 60:5, s. 649-654q 60:5<649-654x 0312-5963x 1179-1926
8564 u https://doi.org/10.1007/s40262-020-00972-1y Fulltext
8564 u https://uu.diva-portal.org/smash/get/diva2:1584234/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 u https://link.springer.com/content/pdf/10.1007/s40262-020-00972-1.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-450118
8564 8u https://doi.org/10.1007/s40262-020-00972-1

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