TABLE 8.
Calculated and predicted pharmacokinetic parameters of tramadol HCl formulations.
| Pharmacokinetic parameters | Immediate release tramadol HCl - 50 mg a | Osmotic controlled-release (CR) tramadol HCl - 190 mg b | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Single dose | Multiple dose (q6h for 24 h) | Once-daily F3 (simulated PK data) | Once-daily F4 (simulated PK data) | |||||||
| in-vivo data (parameters calculated with PKPlus™) | Drug release media (for ACAT model based in-vivo simulation) | |||||||||
| 2-stage c | pH 1.2 | pH 4.5 | pH 6.8 | 2-stage c | pH 1.2 | pH 4.5 | pH 6.8 | |||
| C max (ng/ml) | 275.31 | 406.53 | 364.45 | 355.52 | 373.91 | 360.02 | 390.2 | 371.34 | 406.3 | 394.21 |
| T max (h) | 1.12 | 20.74 | 11.28 | 10.87 | 13.15 | 12.33 | 14.97 | 14.2 | 11.8 | 14.14 |
| AUC t (ng/ml×h) | 1524.9 | 6448.2 | 6176.2 | 5903.3 | 6383.7 | 6189.3 | 6441.9 | 6292.8 | 6515.5 | 6470.1 |
| AUC inf (ng/ml × h) | 2164.1 | 7917.4 | 7388.4 | 7103.2 | 7559.6 | 7422.2 | 7663.8 | 7402.2 | 7827.8 | 7705.7 |
a
Data acquired from Brvar et al. (2014) (9) and processed in PKPlus (Gastroplus™, ver 9.8).
b
The in-vitro release data in various dissolution media (0.1 N HCl pH 1.2, phosphate buffer pH 4.5 and 6.8) was incorporated in ‘ACT’ model in GastroPlus™, for in-vivo pharmacokinetic simulation.
c
2-stage media comprised of 2 h in 0.1 N HCL pH 1.2 and then from 3–24 h in phosphate buffer pH 6.8 (8).