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  • de Rouw, NikkiRadboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands.;Jeroen Bosch Hosp, Dept Pharm, Shertogenbosch, Netherlands. (författare)

Rethinking the Application of Pemetrexed for Patients with Renal Impairment : A Pharmacokinetic Analysis

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-01-09
  • ADIS INT LTD,2021
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-450118
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-450118URI
  • https://doi.org/10.1007/s40262-020-00972-1DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Boosman, Rene J.Netherlands Canc Inst, Dept Pharm & Pharmacol, Amsterdam, Netherlands. (författare)
  • Huitema, Alwin D. R.Netherlands Canc Inst, Dept Pharm & Pharmacol, Amsterdam, Netherlands.;Univ Utrecht, Med Ctr, Dept Clin Pharm, Utrecht, Netherlands. (författare)
  • Hilbrands, Luuk B.Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, Nijmegen, Netherlands. (författare)
  • Svensson, Elin,1985-Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands.(Swepub:uu)elisv718 (författare)
  • Derijks, Hieronymus J.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. (författare)
  • van den Heuvel, Michel M.Radboud Univ Nijmegen, Med Ctr, Dept Pulm Dis, Nijmegen, Netherlands. (författare)
  • Burger, David M.Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands. (författare)
  • ter Heine, RobRadboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, POB 9101, NL-6500 HB Nijmegen, Netherlands. (författare)
  • 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.Netherlands Canc Inst, Dept Pharm & Pharmacol, Amsterdam, Netherlands. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Clinical Pharmacokinetics: ADIS INT LTD60:5, s. 649-6540312-59631179-1926

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