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Table 1 Comparison of rate constants for efflux and clearances for Slc22 and Slco substrates and the perivascular markers inulin, mannitol and sucrose

From: Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

 

keff/min−1

t1/2/min

Vd/mL/g

CL/µL g−1 min−1

Ref #

Notes

Slc substrates

Rat unless stated otherwise

 p-Aminohippuric acid (PAH)

0.059

12

0.80

47

[558]

Influx much slower than efflux

 p-Aminohippuric acid (PAH)

0.039

18

  

[559]

Abl. Oat3 based on inhibitors, lum. Mrp4 possible based on kidney [560]

 p-Aminohippuric acid (PAH)

0.0175

40

  

[131]

 

 Penicillin G, benzylpenicillin

0.043

16

  

[559]

Oat3 based on inhibitors

 Taurocholate

0.023

30

  

[561]

 

 BQ-123

0.0078

100

  

[561]

 

 Estrone sulfate

0.066

9.9

1.1

75

[562]

 

 Estrone

0.061

11

3.3

227

[562]

 

 Dehydroepiandrosterone sulfate (DHEAS)

0.027

26

 

118

[563]

Influx much slower than efflux, Oatp2

 Estradiol-17beta-glucuronide (E217betaG)

0.037

19

  

[564]

Oatp2, 40% and Oat3 20%

 Pravastatin

0.060

12

0.99

59

[565]

Oat3 (Slc22a8) and Oatp2 (Slco1a4) + others

 Pitavastatin

0.026

27

14

364

[565]

Oat3, Oatp2 (Slco1a4) +others +diffusion

 Homovanillic acid

0.017

40.8

  

[566]

Oat3 from inhibitors

 Indoxyl sulfate

0.011

64

  

[567]

Oat3 and others

 Pemetrexed

0.018

39

0.62

11

[568]

Mouse. Oat3 and unknown (not Mrp2 not Bcrp)

 Methotrexate

0.024

29

0.85

20

[568]

Oat3 and Bcrp suggested

 Buprenorphine

0.025

27.5

6.1

154

[569]

Pgp and unknown, possibly diffusion

 AZT, (3′-azido-3′-deoxythymidine)

0.032

22

  

[570]

Oat3 from benzylpenicillin inhibition

 DDI, (2′,3′-dideoxyinosine)

0.253

2.8

  

[570]

Oat3 from benzylpenicillin inhibition + diffusion

Markers for perivascular elimination

 Inulin

0.006 awake

0.016 asleep

115

43

0.2*

1.2

3.2

[128]

Mouse

 Inulin

0.003

230

0.2*

0.6

[62]

Mouse

 Inulin

0.005

135

0.2*

1

[131]

Rat

 Mannitol

0.004

170

0.2*

0.8

[25]

Mouse

 Sucrose

0.0028 awake

0.0043 anesth.

245

160

0.2*

0.56

0.86

[131]

Rat

 Albumin

0.006

115

0.2*

1.2

[131]

Rat

 Dextran-10K

0.0035

197

0.2*

0.7

[131]

Rat

 Dextran-70K

0.004

170

0.2*

0.8

[131]

Rat

  1. keff rate constant for efflux determined from the time course of the decrease in concentration after injection of solute into the parenchyma (brain efflux index for the Slc substrates relative to inulin; these underestimate keff for values less than ~ 0.01 min−1 see [131]); t1/2 = 0.69/(rate constant) is the half-life; Vd, volume of distribution in the parenchyma determined using brain slices (ISF volume for inulin and mannitol); CL = Vd × keff, the clearance. For the Slc substrates more than one transporter in each membrane is likely to be involved in the transport
  2. * Assumed equal to ISF volume
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Fluids and Barriers of the CNS

ISSN: 2045-8118