Bioequivalence assessment of two transdermal delivery systems of fentanyl in healthy Chinese volunteers.

The objective of this study was to investigate the bioequivalence of two formulations (generic preparation and Durogesic patch) of 4.2 mg fentanyl. They were assessed in relative bioavailability in 20 healthy Chinese male volunteers according to a single dose, 2-sequence, crossover randomized design. The two formulations were administered at two treatment days, separated by a washout period of 14 days. Blood samples were collected at specified time intervals over 144 hours post-dosing. Plasma samples were separated and assayed for fentanyl using a sensitive LC-MS/MS method. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The value of two formulations was as follows: Cmax, 0.789 (0.256) and 0.821 (0.278) ng/mL; tmax, 45.3 and 41.2 h; t1/2, 21.5 (8.8) and 22.6 (7.2) h; AUC0-T, 52.5 (18.6) and 55.7 (19.7) ng/mL×h; and AUC0-∞, 54.6 (19.3) and 57.5 (21.1) ng/mL×h, respectively. ANOVA and two one-sided t-test procedures showed no significant difference in log-transformed Cmax, AUC0-T and AUC0-∞ while the 90% confidence interval (CI) of the ratio of the geometric means of their values were also used to assess bioequivalence between the two formulations. Based on these statistical inferences it was concluded that the two formulations exhibited comparable pharmacokinetic profiles and that test formulation is bioequivalent to reference formulation. The point estimate (90% CI) of two formulations was: AUC0-T, 96.7% (85 - 105%); AUC0-∞, 97.5% (89 - 110%); Cmax, 96.2% (91 - 104%); tmax, 97.1% (93 - 101%), respectively.