Addition and Correction pubs.acs.org/molecularpharmaceutics
Correction to “Prediction of Ocular Drug Distribution from Systemic Blood Circulation” Kati-Sisko Vellonen, Esa-Matti Soini, Eva M. del Amo, and Arto Urtti* Mol. Pharmaceutics 2016, 13 (9), 2906−2911. DOI: 10.1021/acs.molpharmaceut.5b00729
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simulated profiles decline slower (tmax between 4−12 h) than the experimental ones (tmax at 2 h). The AUC0−last values differed modestly between simulations and experiments (less than 1.5- and 2.8-fold differences when Vss,ivt was assumed to be 8 and 4 mL, respectively)” is corrected to: The simulated profiles decline similarly to the experimental ones (tmax between 3 and 6 h for simulated and around 2 h for experimental profile). The AUC0−last values differed between simulations and experiments from 2.7- to 3.7-fold difference when assuming Vss,ivt of 8 mL and from 4.5- to 6.1-fold difference when Vss,ivt was assumed to be 4 mL. • On page 2910, the text “The simulations showed high correlation with experimental data, and typically, ocular drug exposure in rabbits and humans could be predicted within a 2-fold error margin” is corrected to: The simulations showed good correlation with experimental data, and typically, ocular drug exposure in rabbits could be predicted within a 2-fold error margin, while in the case of the only human study with cefepime the error was higher (between 2- and 6-fold). In conclusion, the predicted concentration profiles in human vitreous are similar to the experimental concentration profiles with similar tmax though higher AUC0−last values. The predictions are still in acceptable range, within 2- to 6-fold error range, but data for more compounds investigated in human are still needed to draw final conclusions.
n the original article, eq 2 on page 2907 was wrongly written and used: human apparent CL BV = human apparent CL ivt = (rabbit CL ivt − 0.04)/1.41
The correct equation is human apparent CL BV = human apparent CLivt = 1.41 × rabbit CL ivt + 0.04
(2)
The equation was used to calculate distribution clearance (CLBV) of the only drug investigated in humans presented in the article, cefepime (see Chart 1). The new QSPR CLBV value of cefepime in human (0.3168 mL/h) was applied to the simulation model to predict cefepime concentrations in human vitreous. The corresponding modifications in the Supporting Information and the article text are presented below: • In the Supporting Information, in Supplemental Table 1 the value for the QSPR CLBV in human is not 0.111 mL/h but 0.3168 mL/h. • In the Supporting Information, in Supplemental Figure 1, cefepime concentrations in human vitreous after intravenous administration of 1 and 2 g doses are as shown in Figure S1. • On page 2909, Table 1 is corrected with the new values in bold. • On page 2908, the text “The simulated and experimental cefepime concentrations are in the same range, but the Chart 1
© XXXX American Chemical Society
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DOI: 10.1021/acs.molpharmaceut.7b00020 Mol. Pharmaceutics XXXX, XXX, XXX−XXX
Molecular Pharmaceutics
Addition and Correction
Figure S1. Revised Supplemental Figure 1.
Table 1. Experimental and Simulated Cefepime Concentrations and AUC0−12h Values in Human Serum and Vitreous after Intravenous Administration of Cefepime cefepime dose of 1 g time (h)
experimental serum conc (μg/mL)a
simulated serum conc (μg/mL)
0.5 1 2 4 12 AUC0−12h (μg h mL−1)
71.76 ± 7.26 40.83 ± 6.12 18.24 ± 3.87 7.13 ± 1.66 0.71 ± 0.36 164
71.54 41.27 17.93 7.26 0.69 148
time (h)
experimental serum conc (μg/mL)a
simulated serum conc (μg/mL)
0.5 1 2 4 12 AUC0−12h (μg h mL−1)
140.55 ± 13.22 76.81 ± 6.32 38.53 ± 4.81 19.43 ± 5.12 2.01 ± 0.87 355
140.47 76.89 38.35 19.54 1.99 326
a
experimental vitreous conc (μg/mL)a
simulated vitreous conc (μg/mL)b
simulated vitreous conc (μg/mL)c
3.00 4.54 5.80 6.22 5.39 63
1.51 2.32 3.06 3.49 3.45 38
experimental vitreous conc (μg/mL)a
simulated vitreous conc (μg/mL)b
simulated vitreous conc (μg/mL)c
1.13 ± 0.43 2.41 ± 0.55 2.86 ± 0.37 2.22 ± 0.26 0.97 ± 0.3 22
6.36 9.25 11.68 13.05 11.89 135
3.22 4.74 6.16 7.29 7.53 81
0.76 ± 0.08 1.7 ± 0.19 1.91 ± 0.13 1.22 ± 0.29 0.89 ± 0.14 14 cefepime dose 2 g
From ref 16. bVss,ivt = 4 mL. cVss,ivt = 8 mL.
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DOI: 10.1021/acs.molpharmaceut.7b00020 Mol. Pharmaceutics XXXX, XXX, XXX−XXX
