Pharmacokinetics and dose selection of a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles.

A novel, transdermal fentanyl solution (TFS) was developed that delivers sustained concentrations of fentanyl for days following a single application. The pharmacokinetics following a single topical dose was examined. Eighteen adult Beagle dogs were divided into three groups of six dogs (3M, 3F). Each group was administered a single dose of 1.3 (25), 2.6 (50), or 5.2 mg/kg (100 µL/kg) of TFS. The dose was applied to the clipped, ventral abdominal skin using a 1-mL tuberculin syringe. Immediately following dosing, collars were placed on each dog through 72 h to prevent direct licking of the application site. Serial jugular venous blood samples were collected at 0 (predosing), 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 408, and 504 h after dosing and assayed for plasma fentanyl concentration. Fentanyl was rapidly detected following application with a mean absorption lag time (t(lag) ) of 0.333 h in the 1.3 mg/kg group and 0 in the other two groups. The mean C(max) increased with dose and were 2.28, 2.67, and 4.71 ng/mL in the 1.3, 2.6 and 5.2 mg/kg dose groups, respectively. Mean terminal half-lives were 53.7, 69.6, and 103 h in the 1.3, 2.6, and 5.2 mg/kg dose groups, respectively. The mean AUC(0-LLOQ) from lowest to highest dose groups were 157, 268, and 645 ng·h/mL and were dose proportional with a R(2) value of 0.9818. Adverse reactions were limited to the highest dose group and included sedation (four of six dogs) and decreased food and water intake (one dog). A dose of 2.6 mg/kg (50 µL/kg) is proposed for further development studies based on the lack of adverse events that were observed compared to the 5.2 mg/kg group and a more rapid onset of action and longer duration of action compared to the 1.3 mg/kg group.

Pharmacokinetics of spinosad and milbemycin oxime administered in combination and separately per os to dogs.

Pharmacokinetic (PK) studies were conducted to determine the potential PK interactions when spinosad and milbemycin oxime (MBO) are administered simultaneously. Investigations used commercial MBO tablets (C-MBO; Interceptor(®) Flavor Tabs, active ingredient MBO, Novartis Animal Health, Greensboro, NC, USA), novel-source (Elanco) MBO (E-MBO) in a gelatin capsule, spinosad API (Active Pharmaceutical Ingredient using registered manufacturing process) in a gelatin capsule, spinosad tablets (Comfortis(®) chewable beef flavored tablets, active ingredient spinosad, Elanco Animal Health, Greenfield, IN, USA), and the recently registered spinosad + E-MBO combination tablets (Trifexis™ chewable beef flavored tablets, active ingredients E-MBO and spinosad, Elanco Animal Health, Greenfield, IN, USA). Regardless of the source of MBO, in the presence of spinosad, greater systemic exposure of MBO was obtained as compared to MBO administered alone. Target animal safety studies conducted with dose multiples of spinosad and MBO indicate the increased exposure of MBO does not have implications on adverse clinical reactions. Further research is required to determine whether the higher levels of MBO have any implications for improved effectiveness as compared to C-MBO. Effectiveness studies conducted with 0.5 mg/kg of E-MBO in combination tablets demonstrated noninterference against C-MBO with both products achieving >99% effectiveness against the dose-limiting nematode, Ancylostoma caninum. No statistical differences were detected in the PK of MBO when comparing animals receiving E-MBO (without spinosad) and C-MBO. Also, the PK of spinosad was unaltered when co-administered with MBO.

Epicardial pacing after cardiac surgery.

This article focuses on the use of epicardial wires, the different types of pacing therapy, troubleshooting pacemaker problems, as well as the nursing management of the patient receiving epicardial pacing therapy.