TABLE 2

Pharmacokinetic variables of pitavastatin, pioglitazone, repaglinide and their metabolite in eight healthy volunteers when coadministered with a single dose of 600 mg rifampicin, 200 mg trimethoprim, or 300 mg clopidogrel

Data are presented as mean ± S.D. In all plasma samples, the concentration of repaglinide M4 was below the lower limit of quantification (0.01 ng/ml).

VariablesControlRifampicin 600 mgP ValueControlTrimethoprim 600 mgP ValueControlClopidogrel 300 mgP Value
Pitavastatin
 Cmax (ng/ml)3.97 ± 1.3118.7 ± 8.00.0011**3.26 ± 1.352.98 ± 1.580.63012.78 ± 1.622.86 ± 2.130.8840
 tmax (h)0.56 ± 0.180.56 ± 0.181.00000.56 ± 0.180.66 ± 0.400.50400.56 ± 0.180.56 ± 0.181.0000
 AUC0–24h (ng⋅h/ml)8.45 ± 1.7542.7 ± 15.00.0002***7.69 ± 2.207.26 ± 1.450.51506.84 ± 3.327.45 ± 4.340.5779
Pitavastatin lactone
 Cmax (ng/ml)2.82 ± 0.742.16 ± 0.430.0353*2.77 ± 0.842.68 ± 0.680.73663.10 ± 0.972.55 ± 0.680.0570
 tmax (h)1.00 ± 0.000.81 ± 0.260.07961.13 ± 0.441.13 ± 0.441.00001.00 ± 0.001.31 ± 0.370.0492*
 AUC0–24h (ng⋅h/ml)14.2 ± 3.612.6 ± 3.00.261613.4 ± 3.913.5 ± 2.30.924215.6 ± 4.115.9 ± 6.40.8652
Pioglitazone
 Cmax (ng/ml)65.0 ± 11.065.6 ± 11.80.877559.6 ± 13.054.2 ± 11.00.242658.4 ± 10.872.0 ± 12.30.0041**
 tmax (h)1.06 ± 0.561.81 ± 1.390.16351.63 ± 1.272.44 ± 0.820.14151.50 ± 0.802.69 ± 1.100.0460*
 AUC0–24h (ng⋅h/ml)475 ± 81486 ± 820.5859477 ± 87591 ± 840.0096*529 ± 248938 ± 1790.0015**
Pioglitazone M4
 Cmax (ng/ml)19.6 ± 1.522.0 ± 3.70.089719.3 ± 3.114.6 ± 3.90.0050*17.2 ± 5.513.3 ± 3.20.0040**
 tmax (h)16.0 ± 6.820.0 ± 7.40.200220.5 ± 6.624.0 ± 0.00.175516.0 ± 6.824.0 ± 0.00.0123*
 AUC0–24h (ng⋅h/ml)382 ± 37421 ± 760.2725359 ± 72233 ± 790.0007**328 ± 109221 ± 580.0013**
Repaglinide
Cmax (ng/ml)2.36 ± 0.885.82 ± 1.660.0007**2.04 ± 0.802.88 ± 1.140.0332*2.18 ± 0.922.79 ± 1.190.0254*
 tmax (h)0.50 ± 0.230.53 ± 0.210.78490.56 ± 0.180.56 ± 0.401.00000.66 ± 0.400.88 ± 0.580.1334
 AUC0–8h (ng⋅h/ml)2.94 ± 1.287.64 ± 2.860.0005***2.71 ± 1.054.93 ± 1.720.0044**4.01 ± 2.5810.0 ± 5.20.0088*
Repaglinide M1
Cmax (ng/ml)0.10 ± 0.030.13 ± 0.050.13330.08 ± 0.030.08 ± 0.020.71500.08 ± 0.040.07 ± 0.030.7748
 tmax (h)0.69 ± 0.260.50 ± 0.000.07960.66 ± 0.300.88 ± 0.580.21330.75 ± 0.380.94 ± 0.500.4758
 AUC0–2h (ng⋅h/ml)0.12 ± 0.030.14 ± 0.040.38760.09 ± 0.040.09 ± 0.030.90360.09 ± 0.050.10 ± 0.040.4110
  • Cmax, peak plasma concentration; tmax, time to Cmax; AUC0–t, area under the plasma concentration–time curve from 0 to t.

  • * P < 0.05 versus control, **P < 0.005 versus control, ***P < 0.0005 versus control.