Fluids and Barriers of the CNS

Table 2 Free fraction (f_u) determined in vitro and predicted using Eq. 2

From: Application of a new MDCKII-MDR1 cell model to measure the extent of drug distribution in vitro at equilibrium for prediction of in vivo unbound brain-to-plasma drug distribution

Compound	Determined f_u (%)		Predicted f_u (%) *
Compound	Brain (D = 20)	BSA 35 μM (D = 20)	Brain (D = 20)	BSA 35 μM (D = 20)
Altanserin	22.9 ± 1.4	45.1 ± 3.5	22.1	26.8
Antipyrine	84.3 ± 4.2	> 100	> 100	99.9
Atenolol	95.2 ± 2.1	> 100	> 100	99.9
Buspirone	83.6 ± 9.5	84.2 ± 2.9	83.1	90.4
Cimetidine	93.8 ± 5.0	> 100	95.6	99.2
Citalopram	51.3 ± 6.6	97.3 ± 2.7	47.9	96.0
Diphenhydramine	62.6 ± 6.1	> 100	72.8	94.7
Doxepin	24.8 ± 5.0	92.2 ± 2.9	33.0	87.1
Fluoxetine	5.2 ± 0.5	66.0 ± 3.2	5.7	70.6
Gabapentin	94.6 ± 1.5	98.4 ± 6.2	93.4	99.8
Indomethacin	35.8 ± 8.0	19.6 ± 1.2	42.8	38.2
Metoclopramide	87.8 ± 3.8	> 100	90.7	98.8
N-desmethylclozapine	13.1 ± 0.6	89.2 ± 2.9	13.9	82.1
Propranolol	35.0 ± 1.2	89.7 ± 1.8	37.4	86.8
Risperidone	74.5 ± 1.9	91.8 ± 1.6	69.9	89.4
Way-100635	74.8 ± 8.0	80.2 ± 0.9	71.8	87.1

Data represents mean ± SD of one test occasion of three individual filters, ‘n’ denotes test occasions, and ‘total N’ denotes the total number of replicates (n = 1, total N = 3), and predicted f_u are shown as mean values
^* Calculated with use of Eq. 2, see Sect. "In vitro BSA and brain homogenate binding for reference compounds"
D denotes the dilution factor of the matrix

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ISSN: 2045-8118

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