TABLE 4

Uptake clearance of drugs in rat isolated hepatocytes

Time-dependent uptake of drugs in rat isolated hepatocytes was measured in the presence of tracer amount of drugs in the incubation buffer (0.1 μM for [3H]pravastatin, [3H]pitavastatin, [3H]rosuvastatin, [3H]valsartan, and [3H]olmesartan; 6.3 μM for [14C]temocaprilat; 1.7 μM for [14C]PCG; 10 μM for enalaprilat, benazeprilat, ceftizoxime, and cefmetazole). The in vitro intrinsic uptake clearance (P1 hep) was calculated by dividing initial uptake velocity by the drug concentration in the incubation buffer. Each value is expressed as mean ± S.E. of triplicate determinations.


Compound

P1HEP
μl/min/106 cells
Pravastatin 34.3 ± 4.3
Pitavastatin 519 ± 9
Rosuvastatin 201 ± 20
Valsartan 112 ± 15
Olmesartan 45.2 ± 11.3
Candesartan 72.5 ± 3.1
Temocaprilat 18.6 ± 1.1
Enalaprilat 1.19 ± 0.78
Benazeprilat 4.70 ± 0.70
PCG 8.77 ± 2.26
Ceftizoxime 1.30 ± 0.20
Cefmetazole
19.9 ± 5.1