Table 3.
Pharmacokinetic parameters of PMX in rats after intravenous injection of PMX and oral administration of PMX, PMX/DCK, or PMX/DCK-OP
| Test material | PMX | PMX | PMX/DCK | PMX/DCK-OP |
|---|---|---|---|---|
| Administration | Intravenous | Oral | Oral | Oral |
| Dose of PMX (mg/kg) | 5 | 25 | 25 | 25 |
| Tmax (h) | - | 0.63±0.25 | 0.50±0.00 | 0.50±0.00 |
| T1/2 (h) | 0.35±0.08 | 2.50±0.45 | 4.05±2.02 | 2.47±0.37 |
| Cmax (μg/mL) | 15.3±6.10 | 1.28±0.17 | 4.58±2.63 | 5.95±3.23 |
| AUClast (μg/mL) | 9.38±4.17 | 2.35±0.27 | 4.13±1.29 | 9.27±3.25**,# |
| AUCinf (μg/mL) | 9.41±4.22 | 2.77±0.21 | 4.90±1.73 | 10.2±2.94***,# |
| Bioavailability (%) | 5.02±0.57 | 8.80±2.89 | 19.8±6.93**,# |
Notes: Statistics: one-way ANOVA followed by Tukey’s multiple-comparison test. Each value represents the mean ± standard deviation (n=4). Bioavailability (%), (AUClast, oral/DosePMX, oral)/(AUClast, intravenous/DosePMX, intravenous)×100. **P<0.01, ***P<0.001 compared to PMX; #P<0.05 compared to PMX/DCK.
Abbreviations: PMX, pemetrexed; DCK, Nα-deoxycholyl-L-lysyl-methylester; PMX/DCK, ion-pairing complex between PMX and DCK; PMX/DCK-OP, oral powder formulation of PMX/DCK; Tmax, time to reach maximum plasma concentration; T1/2, half-life of plasma concentration; Cmax, maximum plasma concentration; AUClast, area under the plasma concentration-time curve from zero to the time of the last measurable plasma concentration; AUCinf, area under the plasma concentration-time curve from zero to infinity.