BioMed Research International
Volume 2015 (2015), Article ID 124035, 3 pages
http://dx.doi.org/10.1155/2015/124035

Corrigendum

Corrigendum to “Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy”

J. G. Coen van Hasselt,1,2 Karel Allegaert,3,4 Kristel van Calsteren,3,5 Jos H. Beijnen,2,6 Jan H. M. Schellens,1,6 and Alwin D. R. Huitema1,2

¹Department of Clinical Pharmacology, Netherlands Cancer Institute, Plesmanlaan 121, P.O. Box 1066 CX, Amsterdam, Netherlands
²Department of Pharmacy & Pharmacology, Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, P.O. Box 90440, 1006 BK Amsterdam, Netherlands
³Department of Development and Regeneration, KU Leuven, Herestraat 49, 300 Leuven, Belgium
⁴Neonatal Intensive Care Unit, University Hospitals Leuven, Herestraat 49, 300 Leuven, Belgium
⁵Obstetrics and Gynecology, University Hospitals Leuven, Herestraat 49, 300 Leuven, Belgium
⁶Division of Pharmacoepidemiology & Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, P.O. Box 80125, 3508 TC Utrecht, Netherlands

Received 9 March 2015; Accepted 17 March 2015

Copyright © 2015 J. G. Coen van Hasselt et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Our paper “Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy” contains three textual errors we wish to correct. Furthermore we wish to make a textual clarification. The corrections are as follows.

Table 2: the equations in footnotes a and b have been erroneously switched. The correct footnotes should be as follows:Empirical model: .Semiphysiological model: . Figure 1: the units of time in the -axis label are incorrectly labeled as hours. The correct units are minutes; hence the correct -axis label is “Time (min).” Figure 4: the caption of Figure 4 starts incorrectly with “Simulations of typical free and total cefazolin concentration-time ,” while the figure’s -axis labels state “Free cefazolin (mg/L).” The figure actually only depicts free cefazolin. Hence, the caption of Figure 4 should be corrected to “Simulations of typical free cefazolin concentration-time .” Clarification: we would like to make a clarification to the implementation of our model which included free and total cefazolin concentrations. The parameters , , , and were fit based on the free cefazolin concentration. The individual total cefazolin concentrations were then predicted based on the individually predicted free cefazolin concentration together with the estimation of the fraction unbound () (7). Other PK analyses of cefazolin have reported the total cefazolin concentrations. Hence, in order to convert our CL based on unbound cefazolin (CLfree) to CL based on total concentration (CLtotal), multiplication with is necessary: .

These corrections do not influence the results, discussion, or conclusion of this work.

Table 2: Parameter estimates of the base and final population PK models (empirical and semiphysiological) for cefazolin.

Description
Parameter
Unit
Estimates (RSE %)

Base model
Empirical model
CL~GAa
Semiphysiological
model CL~CrCLb

Structural model

    Clearance

L/min
0.49 (7)
0.119 (58)
0.142 (44)

    Central volume

L
32.5 (16)
33.1 (17)
14.1 (25)

    Peripheral volume

L
12.8 (25)
12.8 (27)
17.1 (7)

    Intercompartmental clearance

L/min
0.335 (21)
0.326 (25)
0.436 (10)

    Free fraction

—
0.289 (5)
0.286 (5)
0.291 (9)

    Gestation effect on clearance

—
0.217 (16)
0.212 (38)

Between-subject variability

    Clearance

CV%
22.1 (25)
19.9 (24)
10.4 (70)

    Central volume

CV%
49.1 (22)
47.6 (21)
101.5 (21)

    Peripheral volume

CV%
32.7 (41)
34.2 (41)
68 (26)

    Free fraction

CV%
18.9 (36)
17.5 (37)
19.1 (38)

Residual unexplained variability variances

    Proportional, free concentration

0.0162 (8)
0.0158 (11)
0.0153 (8)

    Additive, free concentration

0.176 (34)
0.229 (42)
0.217 (36)

    Proportional, total concentration

0.0348 (8)
0.0328 (10)
0.0328 (9)

    Additive, total concentration

0.662 (48)
0.842 (46)
0.681 (25)

RSE: relative standard error; GA: gestational age (weeks).

aEmpirical model: .

bSemiphysiological model: .

(a)

(b)

Figure 1: Simulated (areas) and observed (solid circles, lines) free and total cefazolin concentrations versus time as predicted by the empirical model (a) and semiphysiological model (b) for trimesters 2 and 3 of pregnancy. Simulations are represented as the parametric 95% confidence intervals of the simulated 50th (red), 5th, and 95th (blue) percentiles. For the observed values, the 50th (continuous line), 5th, and 95th (dashed lines) percentiles are depicted in red.

Figure 4: Simulations of typical free cefazolin concentration-time profiles using the empirical and the semiphysiological approach at different periods of pregnancy (gestational weeks) based on a dose regimen of 2 g cefazolin every 6 or 8 hours administered over 30 minutes. The expected 90% minimum inhibitory concentration is depicted as horizontal black line. GW: gestational weeks.