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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