uu.seUppsala universitets publikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Population pharmacokinetics of cytarabine, etoposide, and daunorubicin in the treatment for acute myeloid leukemia
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
Visa övriga samt affilieringar
2012 (Engelska)Ingår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 69, nr 5, s. 1155-1163Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Interpatient variability in the pharmacokinetics (PK) of cytarabine, etoposide, and daunorubicin following body surface area-adjusted doses calls for studies that point to other covariates to explain this variability. The purpose of this study was to investigate such relationships and give insights into the PK of this combination treatment. A prospective population PK study of twenty-three patients with acute myeloid leukemia was undertaken. Plasma concentrations of patients were determined by high-pressure liquid chromatography. PK models were developed with NONMEMA (R); for daunorubicin, PK information from a prior study was utilized. Baseline white blood cell count (bWBC) influenced the PK for all drugs. A small, statistically insignificant improvement in model fit was achieved when a relationship between bWBC and daunorubicin central volume of distribution was included. The volume increased 1.9% for each increase in bWBC by 1 x 10(6) cells/mL. The clearances of etoposide and cytarabine were significantly increased and decreased, respectively, by increased bWBC. Tenfold changes in bWBC were needed for these relationships to have potential clinical relevance. A decrease in creatinine clearance of 60 mL/min resulted in a decrease in etoposide clearance of 32%. Population-based models characterized the PK for all three drugs. bWBC was a significant covariate for etoposide and cytarabine and showed a trend for daunorubicin. Linking the significant bWBC relationships and the relationship between kidney function and etoposide clearance to clinical end points would support dose individualization. Patients with above-normal creatinine clearances and high bWBC may receive sub-optimal treatment due to elevated etoposide clearances.

Ort, förlag, år, upplaga, sidor
2012. Vol. 69, nr 5, s. 1155-1163
Nyckelord [en]
Cytarabine, Etoposide, Daunorubicin, Population pharmacokinetics, NONMEM, Acute myeloid leukemia
Nationell ämneskategori
Farmaceutiska vetenskaper
Identifikatorer
URN: urn:nbn:se:uu:diva-174913DOI: 10.1007/s00280-011-1800-zISI: 000303418500005OAI: oai:DiVA.org:uu-174913DiVA, id: diva2:529519
Tillgänglig från: 2012-05-30 Skapad: 2012-05-30 Senast uppdaterad: 2018-01-12Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltext

Personposter BETA

Bender, BrendanFriberg, Lena E.

Sök vidare i DiVA

Av författaren/redaktören
Bender, BrendanFriberg, Lena E.
Av organisationen
Institutionen för farmaceutisk biovetenskap
I samma tidskrift
Cancer Chemotherapy and Pharmacology
Farmaceutiska vetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetricpoäng

doi
urn-nbn
Totalt: 413 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf