Table 2.
Plasma pharmacokinetic parameters of paracetamol, paracetamol glucuronide and paracetamol sulphate following a single p.o. dose of paracetamol of 100 mg/kg
| Pharmacokinetic parametersa | IIIPA M ± SD (CV%) |
IL + PA M ± SD (CV%) |
IL + PA vs. IIIPA p-value |
|---|---|---|---|
| paracetamol | |||
| kel (1/h) | 0.33 ± 0.10 (30.2) |
0.24 ± 0.13 (53.2) |
0.1259b |
| AUC0-∞ (μg × h/mL) | 88.62 ± 8.96 (10.1) |
45.41 ± 21.21 (46.7) |
0.0004c |
| AUC0-t (μg × h/mL) | 80.46 ± 12.10 (15.0) |
34.80 ± 20.07 (57.7) |
<0.0001b |
| Cmax (μg/mL) | 24.70 ± 8.43 (34.1) |
10.93 ± 6.88 (62.9) |
0.0030b |
| t0.5 (h) | 2.26 ± 0.70 (31.0) |
5.30 ± 6.92 (130.7) |
0.0929d |
| Cl/F (L/h) | 0.57 ± 0.06 (9.9) |
1.41 ± 0.87 (61.2) |
0.0008d |
| Vd/F (L) | 1.98 ± 0.63 (31.6) |
8.94 ± 8.04 (89.9) |
0.0023d |
| AUMC0-t (μg × h2/mL) | 203.85 ± 18.15 (8.9) |
97.11 ± 52.00 (53.6) |
0.0023d |
| MRT0-t (h) | 2.57 ± 0.30 (11.5) |
2.88 ± 0.27 (9.3) |
0.0440b |
| paracetamol glucuronide | |||
| AUC0-∞ (μg × h/mL) | 154.08 ± 35.58 (23.09) |
109.94 ± 22.89 (20.8) |
0.0105b |
| AUC0-t (μg × h/mL) | 136.24 ± 23.58 (17.31) |
101.50 ± 22.02 (21.7) |
0.0087b |
| Cmax (μg/mL) | 38.38 ± 3.75 (9.76) |
29.01 ± 7.62 (26.3) |
0.0075b |
| paracetamol glucuronide/paracetamole | |||
| AUC0-∞ | 3.62 ± 1.72 (47.6) |
3.36 ± 2.37 (70.6) |
0.0274c |
| AUC0-t | 1.75 ± 0.47 (27.1) |
3.68 ± 1.67 (45.4) |
0.0209c |
| Cmax | 1.67 ± 0.41 (24.7) |
3.58 ± 1.85 (51.5) |
0.0356c |
| paracetamol sulphate | |||
| AUC0-∞ (μg × h/mL) | 82.42 ± 32.71 (39.7) |
130.23 ± 31.32 (24.1) |
0.0098b |
| AUC0-t (μg × h/mL) | 71.92 ± 31.04 (43.2) |
116.04 ± 27.02 (23.3) |
0.0089b |
| Cmax (μg/mL) | 19.41 ± 7.05 (36.4) |
35.15 ± 6.61 (18.8) |
0.0004b |
| paracetamol sulphate/paracetamolf | |||
| AUC0-∞ | 1.05 ± 0.45 (43.1) |
4.86 ± 2.74 (56.5) |
0.0008c |
| AUC0-t | 0.91 ± 0.43 (47.3) |
4.27 ± 2.29 (53.5) |
0.0008c |
| Cmax | 0.88 ± 0.46 (52.7) |
4.73 ± 3.02 (64.0) |
0.0008c |
aAUC0-t. area under the plasma concentration-time curve from zero to the time of the last measurable concentration; Cmax. maximum plasma concentration; tmax. Time to the first occurrence of Cmax; t0.5. half-life in elimination phase; Cl. clearance (Cl); Vd/kg. volume of distribution per kilogram; AUMC0-t. area under the first moment curve from zero to the time of the last measurable concentration; MRT0-t. mean residence time;
bt-test; cSatterthwaite test; dKruskal-Wallis test; eparacetamol glucuronide/paracetamol ratio; fparacetamol sulphate/paracetamol ratio