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Sökning: WFRF:(Choi Boyoon) > (2013) > Population pharmaco...

  • Kim, In-Wha (författare)

Population pharmacokinetics analysis of cyclophosphamide with genetic effects in patients undergoing hematopoietic stem cell transplantation

  • Artikel/kapitelEngelska2013

Förlag, utgivningsår, omfång ...

  • 2013-04-16
  • Springer Science and Business Media LLC,2013
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-206430
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-206430URI
  • https://doi.org/10.1007/s00228-013-1507-7DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

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

Anmärkningar

  • To build a population pharmacokinetic (PK) model of cyclophosphamide (CY) and its metabolite, 4-hydroxycyclophosphamide (HCY), in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) and to identify covariates, including genetic polymorphisms, which affect CY and HCY PK parameters. The study cohort comprised 21 patients undergoing HSCT who received CY intravenously between 2009 and 2011. Clinical characteristics and CY and HCY concentration data were collected for all patients, and ABCB1, ABCC2, GSTA1, GSTM1, GSTP1, GSTT1, CYP2B6, CYP2C19, and CYP3A5 genotyping was performed. A hypothetical enzyme compartment was conducted using the NONMEM program. A population PK analysis showed that the ABCC2 1249 genotype and aspartate aminotransferase levels significantly affected non-induced clearance (CL (UI)) and induced clearance (CL (I)) of CY, respectively. The final estimate of the mean CL (UI) and CL (I) of CY was 15.5 and 0.683 L/h, respectively, and the mean volume of distribution (V (1)) of CY was 88.0 L. The inter-individual variability for CL (UI), CL (I), and V (1) of CY was 52.8, 200, and 18.0 %, respectively. Additionally, the CL (UI) of CY was significantly decreased to approximately 51 % in patients with the 1249 GA heterozygous genotype compared to those with the 1249 GG wild-type genotype (p < 0.05). There were only three heterozygous GA variants of ABCC2 1249 in the study patients. The population PK model developed in this study implies an influence of genetic factors on the clearance of CY. Clearance was moderately reduced in patients with the ABCC2 1249GA heterozygous genotype.

Ämnesord och genrebeteckningar

  • Cyclophosphamide
  • 4-hydroxycyclophosphamide
  • Population pharmacokinetics
  • Pharmacogenetics
  • Hematopoietic stem cell transplantation

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

  • Yun, Hwi-yeolUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)hwiyu987 (författare)
  • Choi, Boyoon (författare)
  • Han, Nayoung (författare)
  • Kim, Myeong Gyu (författare)
  • Park, Seonyang (författare)
  • Oh, Jung Mi (författare)
  • Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:European Journal of Clinical Pharmacology: Springer Science and Business Media LLC69:8, s. 1543-15510031-69701432-1041

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