Comparison of plasma fentanyl concentrations by using three transdermal fentanyl patch sizes in dogs.

OBJECTIVE

To compare plasma fentanyl concentrations attained after the application of three transdermal fentanyl patch sizes (50, 75, and 100 micrograms/hour) in dogs.

DESIGN

Repeated Latin square controlled study.

ANIMALS

Six intact, mixed-breed adult dogs (2 males, 4 females) weighing 19.9 +/- 3.4 kg.

METHODS

Each dog was randomly assigned to receive each of three treatments: 50 (P50), 75 (P75), or 100 (P100) micrograms/hour transdermal patches. Patches were left in place for 72 hours. Jugular venous blood was collected at 1, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours after patch application and for 1, 2, 4, 8, and 12 hours after patch removal. Plasma fentanyl concentrations were measured using a radioimmunoassay technique. After a 96-hour washout period, each dog was moved to another treatment group and received a different patch size.

RESULTS

The following results were obtained (mean +/- SD): average plasma fentanyl concentration from 24 to 72 hours, 0.7 +/- 0.2 ng/mL (P50), 1.4 +/- 0.5 ng/mL (P75), 1.2 +/- 0.5 ng/mL (P100); the total area under the concentration versus time curve (0 hours to infinity), 46 +/- 12.2 ng/h/mL (P50), 101.2 +/- 41.4 ng/h/mL (P75), 80.4 +/- 38.3 ng/h/mL (P100); and the apparent elimination half-life, 3.6 +/- 1.2 hours (P50), 3.4 +/- 2.7 hours (P75), and 2.5 +/- 2.0 hours (P100). There was a high degree of variability in plasma fentanyl concentrations achieved. Plasma fentanyl concentrations declined rapidly after patch removal.

CONCLUSIONS

The attainment of steady-state plasma concentrations takes up to 24 hours, and there is a great deal of variability in the final concentrations reached in different individuals. In this study, the 100 micrograms/hour patches did not provide statistically increased plasma concentrations when compared with the 50 micrograms/hour patches.

CLINICAL RELEVANCE

Because of the interindividual and intraindividual variation in plasma fentanyl concentrations, patches should be applied 24 hours before the anticipated time that analgesia will be required. Adequacy of analgesia and potentially deleterious side effects, such as sedation and respiratory depression, should be monitored while the patches are in place. Skin reactions may occur, and the patches should be removed if such skin irritation is seen. After the patch is removed, it is expected that analgesia will wane rapidly because of the brief elimination half-life.