Pharmacokinetics and the effect of application site on a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles.
Application of transdermal drugs to different anatomical sites can result in different absorption characteristics. The pharmacokinetics (PKs) and bioequivalence of a single 2.6 mg/kg (50 μL/kg) dose of a novel, long-acting transdermal fentanyl solution were determined when applied topically to the ventral abdominal or dorsal interscapular skin of 40 healthy laboratory Beagles. The PKs were differentiated by a more rapid initial absorption of fentanyl from the dorsal application site. Mean plasma fentanyl concentrations remained above 0.6 ng/mL from 4 to 96 h in the dorsal application group and from 8 to 144 h in the ventral application group. Bioequivalence analysis demonstrated that the sites were not equivalent; the 90% confidence intervals of the ratio of the geometric means for both the maximum concentration (C(max)) and the area under the curve (AUC) were not contained within the 80-125% interval. The C(max) was 2.34 ± 1.29 (mean ± standard deviation) and 2.02 ± 0.84 ng/mL for the ventral and dorsal application groups, respectively. The terminal elimination half-lives (t(1/2)) for both groups were similar with values of 137 ± 58.9 and 117 ± 59.6 h for the ventral and dorsal application site groups, respectively. A mean absorption rate of ≥ 2 μg · kg/h was maintained from 2 to 144 h following dorsal application and from 2 to 264 h following ventral application. These results suggest that transdermal fentanyl solution could be applied as a single dose to the dorsal scapular area 2-4 h prior to surgery with analgesia lasting a minimum of 4 days.
Nexcyon Pharmaceuticals, Inc., Madison, WI 53703, USA.
K J
KJ
Freise
G C
GC
Newbound
C
C
Tudan
T P
TP
Clark
D000042:Absorption; D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D004285:Dogs / Q000378:metabolism*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D010865:Pilot Projects; D012996:Solutions; D013810:Therapeutic Equivalency
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D012996:Solutions; D005283:Fentanyl