Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy
Joint Authors
Schellens, Jan H. M.
van Calsteren, Kristel
Beijnen, Jos H.
Huitema, Alwin D. R.
van Hasselt, J. G. Coen
Allegaert, Karel
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-02-03
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
This work describes a first population pharmacokinetic (PK) model for free and total cefazolin during pregnancy, which can be used for dose regimen optimization.
Secondly, analysis of PK studies in pregnant patients is challenging due to study design limitations.
We therefore developed a semiphysiological modeling approach, which leveraged gestation-induced changes in creatinine clearance (CrCL) into a population PK model.
This model was then compared to the conventional empirical covariate model.
First, a base two-compartmental PK model with a linear protein binding was developed.
The empirical covariate model for gestational changes consisted of a linear relationship between CL and gestational age.
The semiphysiological model was based on the base population PK model and a separately developed mixed-effect model for gestation-induced change in CrCL.
Estimates for baseline clearance (CL) were 0.119 L/min (RSE 58%) and 0.142 L/min (RSE 44%) for the empirical and semiphysiological models, respectively.
Both models described the available PK data comparably well.
However, as the semiphysiological model was based on prior knowledge of gestation-induced changes in renal function, this model may have improved predictive performance.
This work demonstrates how a hybrid semiphysiological population PK approach may be of relevance in order to derive more informative inferences.
American Psychological Association (APA)
van Hasselt, J. G. Coen& Allegaert, Karel& van Calsteren, Kristel& Beijnen, Jos H.& Schellens, Jan H. M.& Huitema, Alwin D. R.. 2014. Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy. BioMed Research International،Vol. 2014, no. 2014, pp.1-9.
https://search.emarefa.net/detail/BIM-506367
Modern Language Association (MLA)
van Hasselt, J. G. Coen…[et al.]. Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy. BioMed Research International No. 2014 (2014), pp.1-9.
https://search.emarefa.net/detail/BIM-506367
American Medical Association (AMA)
van Hasselt, J. G. Coen& Allegaert, Karel& van Calsteren, Kristel& Beijnen, Jos H.& Schellens, Jan H. M.& Huitema, Alwin D. R.. Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-9.
https://search.emarefa.net/detail/BIM-506367
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-506367