Comparative Bioavailability of Tizanidine in Three Dosage Forms (6-MG Delayed-Release Tablets, Sirdalud Preparation, and 2-MG Tablets)

Resumo

Valenta Pharm Co. compared the pharmacokinetic parameters in healthy volunteers of three prototype tizanidine dosage forms (delayed-release 6-mg tablets) and the reference drug sirdalud (2-mg tablets for a total dose of 6 mg, three tablets). This allowed the relative bioavailability of the three prototype tizanidine forms relative to sirdalud to be assessed. All three prototypes showed signs of delay based on MRT parameters of (2.217 ± 0.441) h for the sirdalud instant-release form and (6.529 ± 1.990), (5.951 ± 1.295), and (6.384 ± 2.339) h for prototypes T1, T2, and T3, respectively. High relative exposure levels of prototypes T1, T2, and T3 [AUC 103.80% (73.69 – 146.20), 124.14% (88.14 – 174.86), and 131.93% (93.66 – 185.82), respectively] with a significant decrease of C_max (to 35.83, 38.78, and 40.79%, respectively) were demonstrated by analyzing the comparative bioavailability. A model pharmacokinetic study of the forms produced secondary modeling parameters that were similar to those obtained by an off-model method (89.19 – 122.71%). This confirmed that the developed model was acceptable for planning future clinical tests of these drugs.