Table 1.
Pharmacokinetic parameters of the parent drug diclofenac (1) versus its N-ethoxycarbonylmorpholine ester prodrug (2) in rabbits (n = 6/group). Both drugs were administered orally at a dose of 5 mg/kg for diclofenac, and 7 mg (equimolar dose) of the prodrug (2). None of the pharmacokinetic parameters of the prodrug (2) was different from the corresponding values of the parent drug (p > 0.05; using un-paired t-test).
| AUC0-t | * AUC0-inf | Cmax | Tmax | T 1/2 | Kel | AUC0-t/AUCinf | Kel start | Kel stop | |
|---|---|---|---|---|---|---|---|---|---|
| (ng h/mL) | (ng h/mL) | (ng/mL) | (h) | (h) | (1/h) | (h) | (h) | ||
| Diclofenac sodium (1) | |||||||||
| MEAN | 3188.33 | 3,420.51 | 1,220.8 | 0.61 | 1.69 | 0.45 | 89.38 | 4.40 | 7.20 |
| SD | 1622.77 | 2,247.09 | 383.37 | 0.68 | 0.67 | 0.16 | 7.31 | 1.52 | 1.79 |
| SEM | 662.49 | 1,123.54 | 156.51 | 0.28 | 0.33 | 0.08 | 3.65 | 0.68 | 0.80 |
| CV% | 50.90 | 65.69 | 31.40 | 112.0 | 39.57 | 34.3 | 8.17 | 34.47 | 24.85 |
| N-ethoxycarbonylmorpholine ester prodrug (2) | |||||||||
| MEAN | 3350.20 | 2,796.70 | 1,807.03 | 1.08 | 1.41 | 0.72 | 92.81 | 3.00 | 6.13 |
| SD | 1963.01 | 1,334.75 | 1,537.47 | 0.59 | 0.88 | 0.58 | 6.43 | 1.47 | 2.59 |
| SEM | 801.39 | 667.37 | 627.67 | 0.24 | 0.44 | 0.29 | 3.21 | 0.74 | 1.30 |
| CV% | 58.59 | 47.73 | 85.08 | 54.86 | 61.95 | 80.5 | 6.93 | 49.07 | 42.35 |
* Since some profiles did not show clear elimination and hence did not have AUC infinity data, the average AUC infinity for the prodrug was smaller than average AUC0-t.