TABLE 1

Total plasma, unbound plasma, CSF, and brain concentrations of H2-receptor antagonists after intravenous infusion in rats treated with or without probenecid

H2-receptor antagonists (2 mg/kg) were administered to rats by bolus intravenous administration followed by constant infusion (2 mg/h/kg) during 3 h. Probenecid (15 mg/kg) was administered to rats by bolus intravenous administration followed by constant infusion (30 mg/h/kg) during 3 h, and the unbound plasma concentrations and CSF concentrations of probenecid at 3 h were 154 ± 26 and 57.3 ± 2.0 μM, respectively. Each value represents the mean ± S.D. (n = 3).

Cimetidine
Ranitidine
Famotidine
Control
+Probenecid
Control
+Probenecid
Control
+Probenecid
Cp (μM) 3.71 ± 1.20 2.97 ± 0.15 2.65 ± 1.25 2.11 ± 0.18 3.47 ± 1.22 2.79 ± 0.03
Cp,fu (μM) 2.25 ± 0.60 1.89 ± 0.11 1.72 ± 0.49 1.52 ± 0.06 2.01 ± 0.72 1.54 ± 0.18
CCSF (nM) 39.1 ± 19.8 116 ± 17** 25.9 ± 12.0 97.1 ± 5.2*** 23.1 ± 9.2 43.9 ± 4.1*
Cbrain (nM) 96.5 ± 27.1 99.9 ± 12.5 85.7 ± 33.8 83.9 ± 10.9 106 ± 30 102 ± 18
CCSF/Cp,fu ratio
0.0166 ± 0.005
0.0615 ± 0.0121**
0.0147 ± 0.0046
0.0639 ± 0.0046***
0.0114 ± 0.0027
0.0289 ± 0.0057**

  • Cp, total plasma concentration; Cp,fu, unbound plasma concentration; CCSF, CSF concentration; Cbrain, brain concentration.

    *p < 0.05, **p < 0.01, and ***p < 0.001, significantly different from control rats (unpaired t test).