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A Population Pharma...
A Population Pharmacokinetic-Pharmacodynamic Model of Pegfilgrastim
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- Brekkan, Ari (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmetheus, Uppsala, Sweden,Farmakometri
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- Lopez-Lazaro, Luis (författare)
- Dr Reddys Labs, Basel, Switzerland
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- Yngman, Gunnar (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmetheus, Uppsala, Sweden;Uppsala Univ, Dept Pharmaceut Biosci, Pharmacometr Res Grp, Uppsala, Sweden,Farmakometri
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- Plan, Elodie L. (författare)
- Pharmetheus, Uppsala, Sweden
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- Acharya, Chayan (författare)
- Pharmetheus, Uppsala, Sweden
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- Hooker, Andrew, 1973- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmetheus, Uppsala, Sweden,Farmakometri
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- Kankanwadi, Suresh (författare)
- Dr Reddys Labs, Basel, Switzerland
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- Karlsson, Mats O (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmetheus, Uppsala, Sweden,Farmakometri
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(creator_code:org_t)
- 2018-08-15
- 2018
- Engelska.
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Ingår i: AAPS Journal. - : SPRINGER. - 1550-7416. ; 20:5
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Neutropenia and febrile neutropenia (FN) are serious side effects of cytotoxic chemotherapy which may be alleviated with the administration of recombinant granulocyte colony-stimulating factor (GCSF) derivatives, such as pegfilgrastim (PG) which increases absolute neutrophil count (ANC). In this work, a population pharmacokinetic-pharmacodynamic (PKPD) model was developed based on data obtained from healthy volunteers receiving multiple administrations of PG. The developed model was a bidirectional PKPD model, where PG stimulated the proliferation, maturation, and margination of neutrophils and where circulating neutrophils in turn increased the elimination of PG. Simulations from the developed model show disproportionate changes in response with changes in dose. A dose increase of 10% from the 6 mg therapeutic dose taken as a reference leads to area under the curve (AUC) increases of similar to 50 and similar to 5% for PK and PD, respectively. A full random effects covariate model showed that little of the parameter variability could be explained by sex, age, body size, and race. As a consequence, little of the secondary parameter variability (C-max and AUC of PG and ANC) could be explained by these covariates.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- full random effects modeling
- granulocyte colony-stimulating factor
- pegfilgrastim
- population pharmacokinetic-pharmacodynamic model
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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