Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)
British Journal of Clinical Pharmacology 2013-Sep

Population pharmacokinetic-pharmacodynamic analysis for eribulin mesilate-associated neutropenia.

Samo registrirani korisnici mogu prevoditi članke
Prijava Registriraj se
Veza se sprema u međuspremnik
J G Coen van Hasselt
Anubha Gupta
Ziad Hussein
Jos H Beijnen
Jan H M Schellens
Alwin D R Huitema

Ključne riječi

Sažetak

OBJECTIVE

Eribulin mesilate is an inhibitor of microtubule dynamics that is approved for the treatment of late-stage metastatic breast cancer. Neutropenia is one of the major dose-limiting adverse effects of eribulin. The objective of this analysis was to develop a population pharmacokinetic-pharmacodynamic model for eribulin-associated neutropenia.

METHODS

A combined data set of 12 phase I, II and III studies for eribulin mesilate was analysed. The population pharmacokinetics of eribulin was described using a previously developed model. The relationship between eribulin pharmacokinetic and neutropenia was described using a semi-physiological lifespan model for haematological toxicity. Patient characteristics predictive of increased sensitivity to develop neutropenia were evaluated using a simulation framework.

RESULTS

Absolute neutrophil counts were available from 1579 patients. In the final covariate model, the baseline neutrophil count (ANC0) was estimated to be 4.03 × 10(9) neutrophils l(-1) [relative standard error (RSE) 1.2%], with interindividual variability (IIV, 37.3 coefficient of variation % [CV%]). The mean transition time was estimated to be 109 h (RSE 1.8%, IIV 13.9CV%), the feedback constant (γ) was estimated to be 0.216 (RSE 1.4%, IIV 12.2CV%), and the linear drug effect coefficient (SLOPE) was estimated to be 0.0451 μg l(-1) (RSE 3.2%, IIV 54CV%). Albumin, aspartate transaminase and receival of granulocyte colony-stimulating factor (G-CSF) were identified as significant covariates on SLOPE, and albumin, bilirubin, G-CSF, alkaline phosphatase and lactate dehydrogenase were identified as significant covariates on mean transition time.

CONCLUSIONS

The developed model can be applied to investigate optimal treatment strategies quantitatively across different patient groups with respect to neutropenia. Albumin was identified as the most clinically important covariate predictive of interindividual variability in the neutropenia time course.

Pridružite se našoj
facebook stranici

Najkompletnija baza ljekovitog bilja potpomognuta znanošću

  • Radi na 55 jezika
  • Biljni lijekovi potpomognuti znanošću
  • Prepoznavanje bilja slikom
  • Interaktivna GPS karta - označite bilje na mjestu (uskoro)
  • Pročitajte znanstvene publikacije povezane s vašom pretragom
  • Pretražite ljekovito bilje po učincima
  • Organizirajte svoje interese i budite u toku s istraživanjem vijesti, kliničkim ispitivanjima i patentima

Upišite simptom ili bolest i pročitajte o biljkama koje bi mogle pomoći, unesite travu i pogledajte bolesti i simptome protiv kojih se koristi.
* Svi podaci temelje se na objavljenim znanstvenim istraživanjima

Google Play badgeApp Store badge