Objective—To compare the cardiopulmonary effects of continuous rate infusions (CRIs) of alfaxalone-2-hydroxypropyl-β-cyclodextrin (HPCD) and propofol in healthy dogs.
Animals—6 young adult medium-sized healthy crossbred dogs.
Procedures—A crossover design was used with a washout period of 6 days between anesthetic treatments. Each dog was sedated with acepromazine (0.02 mg/kg, IV) and hydromorphone (0.05 mg/kg, IV). Anesthesia was induced with propofol (4 mg/kg) or alfaxalone-HPCD (2 mg/kg). After endotracheal intubation, anesthesia was maintained with the same agent (propofol, 0.25 mg/kg/min; alfaxalone-HPCD, 0.07 mg/kg/min) for 120 minutes. Dogs spontaneously breathed 100% oxygen. Measurements included end-tidal partial pressure of carbon dioxide, heart and respiratory rates, mean arterial blood pressure, thermodilution-derived cardiac output, and body temperature. Paired arterial and mixed venous blood samples were collected for determination of blood pH, PaCO2, and PaO2. Data were recorded prior to induction; 5, 15, 30, 60, 90, and 120 minutes after induction of anesthesia; and 20 minutes after stopping the CRI, when feasible. Stroke volume and systemic vascular resistance were calculated. Quality of anesthetic induction and recovery and interval to recovery were recorded.
Results—Both propofol and alfaxalone-HPCD produced excellent induction of anesthesia, maintenance, and recovery. Respiratory depression was evident with both anesthetics. Clinically acceptable, mild hemodynamic changes were similar for both anesthetics.
Conclusions and Clinical Relevance—Alfaxalone-HPCD produced clinically acceptable anesthetic quality and hemodynamic values ideal for use as a CRI. Ventilation may need to be supported if hydromorphone is used at these propofol and alfaxalone-HPCD infusion rates.
Objective—To determine bioavailability, pharmacokinetics,
and safety for transdermal (TD) and oral
administration of fluoxetine hydrochloride to healthy
Animals—12 healthy mixed-breed sexually intact
1- to 4-year-old purpose-bred cats.
Procedure—A single-dose pharmacokinetic study
involving 3 groups of 4 cats each was conducted in
parallel. Fluoxetine in a formulation of pluronic lecithin
organogel (PLO gel) was applied to the hairless portion
of the pinnae of cats at 2 dosages (5 or 10
mg/kg), or it was administered orally in capsules at a
dosage of 1 mg/kg. Plasma samples were obtained
and submitted for liquid chromatography-mass spectrometry-
mass spectrometry analysis of fluoxetine
and its active metabolite, norfluoxetine.
Results—Peak fluoxetine concentration (Cmax) was
lower and time to Cmax longer for TD administration
versus oral administration. Relative bioavailability of
each dose administered via the TD route was 10% of
the value for oral administration of the drug. Mean
plasma elimination half-life after oral administration
was 47 and 55 hours for fluoxetine and norfluoxetine,
Conclusions and Clinical Relevance—This study
provides evidence that fluoxetine in a 15% (wt:vol)
PLO gel formulation can be absorbed through the skin
of cats into the systemic circulation. However, the relative
bioavailability for TD administration is approximately
only 10% of that for the oral route of administration.
(Am J Vet Res 2003;64:994–998)
Objective—To evaluate whether the leukotriene (LT)
D4 receptor antagonist L-708,738 is therapeutically
beneficial in treating horses with recurrent airway
Animals—12 adult horses with heaves and healthy
lung lobes from 20 slaughtered horses.
Procedure—Lung lobes were used for smooth muscle
tension and radioligand binding studies. Horses
with heaves were given a placebo for 14 days and
administered L-708,738 (n = 6; 2.5 mg/kg PO, q 12 h)
or dexamethasone (6; 0.04 mg/kg, IV, q 24 h) from
days 14 to 28. Pulmonary function was measured
weekly for 36 days, and bronchoalveolar cells were
collected on days 0, 14, and 29 for cytologic examination.
Results—Nanomolar concentrations of L-708,738
were effective at antagonizing LTD4-induced bronchoconstriction
and LTD4-receptor binding in lung
lobes. Mean peak and trough L-708,738 plasma concentrations
during the treatment period were 1.54 and
0.28 μM, respectively. On days 21 and 29, lung
mechanics were significantly improved in the dexamethasone-
treated horses but not in the L-708,738-treated
horses. Neither dexamethasone nor
L-708,738 had a significant effect on cytologic findings.
Conclusions and Clinical Relevance—L-708,738
was bioavailable after oral administration and sustained
concentrations in plasma during the dosing
period that exceeded in vitro efficacy values.
However, airway function did not improve, suggesting
that either drug concentrations in the lungs were subtherapeutic
or that cysteinyl LT may not be important
mediators of airway inflammation in heaves. Results
provide the first evidence of cysteinyl LT1 receptors in
airways of horses. (Am J Vet Res 2002;63:579–585)