Relationship between Serum Fentanyl Concentration and Transdermal Fentanyl Dosage, and Intra-individual Variability in Fentanyl Concentration after Application of Fentanyl Patches in Patients with Cancer Pain

It has been reported that fentanyl is released from transdermal fentanyl at a constant rate,the concentration reaches a steady state within 24 hours,and a constant serum concentration of the drug can be maintained through repeated patch application at 72-hour intervals.However,we have encountered a number of patients who experienced pain on the third day after application of the patch,and who were not able to gain satisfactory pain relief even when the dosage was increased.In the current study,serum concentrations of fentanyl were determined to elucidate the relationship between fentanyl concentration and transdermal fentanyl dosage,and intra-individual variability in fentanyl serum concentration after fetanyl patch application in patients with cancer pain.Blood samples were collected from 38 patients at 24,48,and 72 hours since the second or later application of the fentanyl patch.A good correlation was obtained between the dose of transdermal fentanyl and the fentanyl serum concentrations(r=0.9565,0.8785 and 0.9351 at 19-30,45-55 and 65-79 hours,respectively,after patch application).When the intra-individual variabilities in serum concentrations were examined,significant differences were noted between 45-52 and 19-25 hours,between 65-72 and 19-25 hours,and between 65-72 and 45-52 hours after application of patches in a paired analysis of variance(P =0.0038,P <0.0001,and P =0.0029,respectively),showing that fentanyl serum concentrations declined between 24 and 72 hours after application of the patch.These findings indicate that in the steady state,fentanyl serum concentrations may not be maintained at a constant level for 3 days following application of transdermal fentanyl,and that the analgesic effect of the drug may be attenuated by 72 hours after applying the patch.