uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för farmakokinetik och läkemedelsterapi.
Vise andre og tillknytning
2002 (engelsk)Inngår i: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 72, nr 3, s. 265-275Artikkel i tidsskrift (Annet vitenskapelig) Published
Abstract [en]

OBJECTIVES: Our objective was to build population pharmacokinetic models that describe plasma concentrations of irinotecan (CPT-11) and its metabolites 7-ethyl-10-hydroxycamptothecin (SN-38) and SN-38 glucuronide (SN-38G) and to investigate the pharmacokinetic-pharmacodynamic relationships between drug exposure and diarrhea, the major dose-limiting toxicity. METHODS: Data were obtained from 109 patients (65 men and 44 women) who received 1.5-hour (range, 0.75- to 2.25-hour) intravenous infusions of irinotecan at doses that ranged from 100 to 350 mg/m(2); 44 patients had a second course. The population pharmacokinetic models were developed to describe plasma concentration-time profiles. The area under the concentration-time curve from time zero to 60 hours [AUC (0-60)] was used as a measure of drug exposure to model the probabilities of diarrhea with use of a logistic regression model. RESULTS: A 3-compartment pharmacokinetic model best described the disposition of irinotecan, whereas SN-38 and SN-38G showed 2-compartmental characteristics. The population estimate of clearance for irinotecan was 31.6 L/h, and the volume of distribution at steady-state (V(SS)) was 263 L. The clearance divided by formation fraction (F(m)) was 712 L/h and 66.8 L/h for SN-38 and SN-38G, respectively. The V(SS)/F(m) was 72,000 L for SN-38 and 85.4 L for SN-38G. The frequencies of diarrhea scores in this study were 46% (grade 0), 28% (grade 1), 20% (grade 2), 4% (grade 3), and 2% (grade 4). Significant correlations between AUC(0-60) and diarrhea scores were found for irinotecan (P <.05) and SN-38G (P <.01) but not for SN-38 or the biliary index. CONCLUSIONS: In this population analysis, irinotecan and SN-38G AUC values were appropriate predictors of the risk for diarrhea, and SN-38G AUC showed the stronger relationship of the two. The developed population models may be useful in further clinical development of this agent.

sted, utgiver, år, opplag, sider
2002. Vol. 72, nr 3, s. 265-275
Emneord [en]
Adult, Aged, Antineoplastic Agents/adverse effects/blood/pharmacokinetics, Area Under Curve, Camptothecin/*adverse effects/*analogs & derivatives/blood/*pharmacokinetics, Chi-Square Distribution, Diarrhea/blood/*chemically induced, Dose-Response Relationship; Drug, Female, Glucuronates/adverse effects/blood/pharmacokinetics, Humans, Male, Middle Aged, Research Support; Non-U.S. Gov't
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-73303DOI: 10.1067/mcp.2002.126741PubMedID: 12235447OAI: oai:DiVA.org:uu-73303DiVA, id: diva2:101213
Tilgjengelig fra: 2005-06-01 Laget: 2005-06-01 Sist oppdatert: 2018-01-14bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekstPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=12235447&dopt=Citation

Personposter BETA

Karlsson, Mats O

Søk i DiVA

Av forfatter/redaktør
Karlsson, Mats O
Av organisasjonen
I samme tidsskrift
Clinical Pharmacology and Therapeutics

Søk utenfor DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 510 treff
RefereraExporteraLink to record
Permanent link

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