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Sökning: id:"swepub:oai:DiVA.org:uu-370009" > Valganciclovir Phar...

  • Tängdén, ThomasUppsala universitet,Infektionssjukdomar (författare)

Valganciclovir Pharmacokinetics in Patients Receiving Oral Prophylaxis Following Kidney Transplantation and Model-Based Predictions of Optimal Dosing Regimens

  • Artikel/kapitelEngelska2018

Förlag, utgivningsår, omfång ...

  • 2018-03-15
  • Springer Science and Business Media LLC,2018
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-370009
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-370009URI
  • https://doi.org/10.1007/s40262-018-0638-5DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

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

Anmärkningar

  • Background and ObjectivesValganciclovir is used as oral prophylaxis for cytomegalovirus (CMV) infection in kidney transplant recipients. However, limited pharmacokinetic data exist to guide dosing in this patient group. This study aimed to describe the population pharmacokinetics of valganciclovir in a large sample of kidney transplant recipients and predict optimal dosing based on Monte Carlo simulations.MethodsTherapeutic drug monitoring (TDM) data from adult kidney transplant recipients who received valganciclovir prophylaxis during a 10-year study period were collected retrospectively. A non-parametric pharmacokinetic analysis and Monte Carlo simulations to determine the probabilities of reaching an area under the drug concentration-time curve (AUC) target of 40-50mgh/L with various dosing regimens at different levels of renal function were conducted using the Pmetrics package for R.ResultsThis study included 792 ganciclovir concentration measurements derived from 97 patients. A one-compartment oral absorption model best described the data. The final covariate model was as follows: CL(ganciclovir)=TVCLx(CLCR/51)(0.75), where CL is the clearance, TVCL is the typical value of ganciclovir clearance, creatinine clearance (CLCR) according to the Cockcroft-Gaultt equation and 51 is the mean CLCR determined in the study. In the simulations, the probability of reaching the targeted AUC was insufficient when using the recommended dosing regimens for prophylaxis, especially in patients with impaired renal function at CLCR<50mL/min.ConclusionsHigher doses of valganciclovir corrected to renal function are suggested for use as oral prophylaxis for CMV infection in kidney transplant recipients. Further study is required to establish TDM targets to ensure adequate drug concentrations while avoiding potentially toxic drug exposures.

Ämnesord och genrebeteckningar

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

  • Cojutti, Pier GiorgioSanta Maria della Misericordia Univ, Inst Clin Pharmacol, ASUIUD, Udine, Italy;Univ Udine, Dept Med, Udine, Italy (författare)
  • Roberts, Jason A.Royal Brisbane & Womens Hosp, Dept Intens Care Med, Brisbane, Qld, Australia;Royal Brisbane & Womens Hosp, Dept Pharm, Brisbane, Qld, Australia;Univ Queensland, Ctr Clin Res, Fac Med, Level 3,Ned Hanlon Bldg, Herston, Qld 4029, Australia;Univ Queensland, Ctr Antiinfect Translat Pharmacodynam, Sch Pharm, Level 3,Ned Hanlon Bldg, Herston, Qld 4029, Australia (författare)
  • Pea, FedericoSanta Maria della Misericordia Univ, Inst Clin Pharmacol, ASUIUD, Udine, Italy;Univ Udine, Dept Med, Udine, Italy (författare)
  • Uppsala universitetInfektionssjukdomar (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Clinical Pharmacokinetics: Springer Science and Business Media LLC57:11, s. 1399-14050312-59631179-1926

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