Table 1

Effect of CsA on Rho123 clearance under a steady-state plasma concentration of Rho123 in untreated and DEX-pretreated rats

Parameter for Rho123UntreatedDEX-Pretreated
Without CsAWith CsAWithout CsAWith CsA
Infusion rate (nmol/min)3.333.333.333.33
Cpss (μM)0.22  ± 0.040.27  ± 0.040.17  ± 0.010.23  ± 0.02
CLtotal(ml/min/kg)68.2  ± 8.657.8  ± 8.681.0  ± 6.464.5  ± 4.6
Intestinal exsorption rate (nmol/min/kg)1.06  ± 0.080.44  ± 0.101-a 1.52  ± 0.130.59  ± 0.011-a
CLexp (ml/min/kg)4.71  ± 0.281.63  ± 0.091-a 8.89  ± 0.771-b 2.77  ± 0.301-a
Biliary excretion rate (nmol/min/kg)0.56  ± 0.080.02  ± 0.011-a 0.30  ± 0.051-b 0.02  ± 0.011-a
CLbile(ml/min/kg)2.93  ± 0.380.06  ± 0.011-a 1.71  ± 0.201-b 0.07  ± 0.021-a
Hepatic concentration (nmol/g)3.51  ± 0.46N.D.2.31  ± 0.201-b N.D.
CLbile * (g liver/min/kg)0.14  ± 0.03N.D.0.13  ± 0.03N.D.

DEX-pretreated rats were given DEX (100 mg/kg/day) orally for 2 consecutive days and used 24 h after the last dosing. After the control-phase clearance study, CsA was injected intravenously at a dose of 30 mg/kg. Each value represents the means ± S.E. (n = 5).

  • N.D., not determined.

  • 1-aP < 0.05, significantly different from the values in the absence of CsA.

  • 1-bP < 0.05, significantly different from the values for untreated rats.