[Usefulness of SPLINE-Deconvolution Method to Analyze Absorption Kinetics of Fentanyl Released from Systemically...

Durotep^®MT Patch (DMTP) (Janssen Pharmaceutical K.K., Tokyo) is a systemically acting narcotic patch containing fentanyl. It is applied transdermally and removed 72 h after applying. The range of effective serum fentanyl concentrations is very narrow (0.3-3 ng/mL). Therefore, analysis of the absorption kinetics (ABK) is especially important. We studied ABK for fentanyl from DMTP 16.8 mg. There are 5 analytical methods to obtain ABK: The estimated mean absorbed rate at steady state (EMARSS) obtained using the residual method (standard value), absolute bioavailability method, Wagner-Nelson method, 3-compartment model Loo-Riegelman method (3LR), and SPLINE-Deconvolution method (SDecon), yielding results of 0.104, 0.119, 0.114, 0.109, and 0.103 mg/h respectively. EMARSS for 3LR and SDecon were nearly equal to the standard value. The absorbed rate for fentanyl with elapsed time by SDecon indicated an amplitude of 3 times with about a 20 h period at 10.7-72 h and the increase in the absorption rate began before the increase in the serum concentration when DMTP was applied transdermally. This phenomenon indicates that the mean absorption rate was constant; thus, an absorption steady state was reached. The actual mean absorption rate during this period was 0.0924 mg/h (range: 0.0594-0.131). The cumulative absorption ratio increased gradually with only a small amplitude, and bioavailability was 44.2%. From our results, SPLINE-Deconvolution is the most suitable method to assess fentanyl absorption kinetics of DMTP.