Objective—To compare pharmacokinetic and pharmacodynamic
characteristics of fentanyl citrate after IV or
transdermal administration in cats.
Animals—6 healthy adult cats with a mean weight of
Procedure—Each cat was given fentanyl IV
(25 mg/cat; mean ± SD dosage, 7.19 ± 1.17 mg/kg
of body weight) and via a transdermal patch (25 µg
of fentanyl/h). Plasma concentrations of fentanyl
were measured by use of radioimmunoassay.
Pharmacokinetic analyses of plasma drug concentrations
were conducted, using an automated curvestripping
process followed by nonlinear, leastsquares
regression. Transdermal delivery of drug
was calculated by use of IV pharmacokinetic data.
Results—Plasma concentrations of fentanyl given IV
decreased rapidly (mean elimination half-life,
2.35 ± 0.57 hours). Mean ± SEM calculated rate of
transdermal delivery of fentanyl was 8.48 ± 1.7 mg/h
(< 36% of the theoretical 25 mg/h). Median steadystate
concentration of fentanyl 12 to 100 hours after
application of the transdermal patch was 1.58 ng/ml.
Plasma concentrations of fentanyl < 1.0 ng/ml were
detected in 4 of 6 cats 12 hours after patch application,
5 of 6 cats 18 and 24 hours after application,
and 6 of 6 cats 36 hours after application.
Conclusions and Clinical Relevance—In cats,
transdermal administration provides sustained plasma
concentrations of fentanyl citrate throughout a 5-
day period. Variation of plasma drug concentrations
with transdermal absorption for each cat was pronounced.
Transdermal administration of fentanyl has
potential for use in cats for long-term control of pain
after surgery or chronic pain associated with cancer.
(Am J Vet Res 2000;61:672–677)
Objective—To evaluate the stability of 3 extemporaneous oral suspensions of enrofloxacin mixed with readily available flavoring vehicles when stored at room temperature (approx 22°C).
Samples—3 commonly compounded oral suspensions of enrofloxacin.
Procedures—On day 0, commercially available enrofloxacin tablets were compounded with a mixture of distilled water and corn syrup (formulation A) or cherry syrup (formulation B) flavoring vehicles to create suspensions with a nominal enrofloxacin concentration of 22.95 mg/mL, and 2.27% enrofloxacin injectable solution was compounded with a liquid sweetener (formulation C) to create a suspension with a nominal enrofloxacin concentration of 11.35 mg/mL. Preparations were stored in amber-colored vials at room temperature for 56 days. For each preparation, the enrofloxacin concentration was evaluated with high-performance liquid chromatography at prespecified intervals during the study. The pH, odor, and consistency for all suspensions were recorded at the start and completion of the study.
Results—Relative to the nominal enrofloxacin concentration, the enrofloxacin concentration strength ranged from 95.80% to 100.69% for formulation A, 108.44% to 111.06% for formulation B, and 100.99% to 103.28% for formulation C. A mild pH increase was detected in all 3 suspensions during the study.
Conclusions and Clinical Relevance—Results indicated that, when stored in amber-colored vials at room temperature for 56 days, the enrofloxacin concentration strength in all 3 formulations was retained within acceptance criteria of 90% to 110%. Subjectively, cherry syrup flavoring was better at masking the smell and taste of enrofloxacin than were the other mixing vehicles.
Objective—To compare the pharmacokinetic properties and bioavailability following oral and IV administration of bisoprolol, a second-generation β1-adrenoceptor–selective blocking agent, with those of carvedilol, a third-generation β1/β2 and α1-adrenoceptor blocking agent, in dogs.
Animals—12 healthy adult Beagles.
Procedures—A prospective, parallel group study was performed. The dogs were allocated to 1 of 2 groups (6 dogs/group) and were administered orally a 1 mg/kg dose of either bisoprolol or carvedilol. Following a 1-week washout period, each cohort received a 1 mg/kg dose of the same drug IV. Blood samples were collected before and after drug administration, and serum concentrations, pharmacokinetic variables, and bioavailability for each agent were assessed.
Results—After oral administration of bisoprolol, the geometric mean value of the area under the concentration-time curve extrapolated to infinity (AUCinf) was 2,195 μg/L (coefficient of variation [CV], 15%). After IV administration of bisoprolol, the dose-normalized geometric mean AUCinf was 2,402 μg/L (CV, 19%). Oral bioavailability of bisoprolol was 91.4%. After oral administration of carvedilol, the geometric mean AUCinf was 70 μg/L (CV, 81%). After IV administration of carvedilol, the geometric mean AUCinf was 491 μg/L (CV, 23%). Oral bioavailability of carvedilol was 14.3%. Total body clearance was low (0.42 L/h/kg) for bisoprolol and high (2.0 L/h/kg) for carvedilol.
Conclusions and Clinical Relevance—After oral administration, carvedilol underwent extensive first-pass metabolism and had limited bioavailability; bisoprolol had less first-pass effect and higher bioavailability. Collectively, these differences suggested that, in dogs, bisoprolol has less interindividual pharmacokinetic variability, compared with carvedilol.