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Abstract

Objective—To determine the pharmacokinetics and effects of orally administered fluconazole in African grey parrots.

Animals—40 clinically normal Timneh African grey parrots (Psittacus erithacus timneh).

Procedure—In single-dose trials, parrots were placed into groups of 4 to 5 birds each and fluconazole was administered orally at 10 and 20 mg/kg. Blood samples for determination of plasma fluconazole concentrations were collected from each group at 2 or 3 of the following time points: 1, 3, 6, 9, 12, 24, 31, 48, and 72 hours. In multiple-dose trials, fluconazole was administered orally to groups of 5 birds each at doses of 10 and 20 mg/kg every 48 hours for 12 days. Trough plasma concentrations were measured 3 times during treatment. Groups receiving 20 mg/kg were monitored for changes in plasma biochemical analytes, and blood samples were collected on days 1 and 13 of treatment to allow comparison of terminal half-life.

Results—Peak plasma concentrations of fluconazole were 7.45 and 18.59 μg/mL, and elimination half-lives were 9.22 and 10.19 hours for oral administration of 10 and 20 mg/kg, respectively. Oral administration of fluconazole for 12 days at 10 or 20 mg/kg every 48 hours did not cause identifiable adverse effects or change the disposition of fluconazole.

Conclusions and Clinical Relevance—Oral administration of fluconazole to parrots at 10 to 20 mg/kg every 24 to 48 hours maintains plasma concentrations above the minimum inhibitory concentration for several common yeast species. The prolonged dosing interval is an advantage of this treatment regimen.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine pharmacokinetics and adverse effects after voriconazole administration to cats and identify an oral dose of voriconazole for cats that maintains plasma drug concentrations within a safe and effective range.

ANIMALS 6 healthy cats.

PROCEDURES Voriconazole (1 mg/kg, IV) was administered to each cat (phase 1). Serial plasma voriconazole concentrations were measured for 24 hours after administration. Voriconazole suspension or tablets were administered orally at 4, 5, or 6 mg/kg (phase 2). Plasma voriconazole concentrations were measured for 24 hours after administration. Pharmacokinetics of tablet and suspension preparations was compared. Finally, an induction dose of 25 mg/cat (4.1 to 5.4 mg/kg, tablet formulation), PO, was administered followed by 12.5 mg/cat (2.05 to 2.7 mg/kg), PO, every 48 hours for 14 days (phase 3). Plasma voriconazole concentration was measured on days 2, 4, 8, and 15.

RESULTS Voriconazole half-life after IV administration was approximately 12 hours. Maximal plasma concentration was reached within 60 minutes after oral administration. A dose of 4 mg/kg resulted in plasma concentrations within the target range (1 to 4 μg/mL). Adverse effects included hypersalivation and miosis. During long-term administration, plasma concentrations remained in the target range but increased, which suggested drug accumulation.

CONCLUSIONS AND CLINICAL RELEVANCE Voriconazole had excellent oral bioavailability and a long half-life in cats. Oral administration of a dose of 12.5 mg/cat every 72 hours should be investigated. Miosis occurred when plasma concentrations reached the high end of the target range. Therefore, therapeutic drug monitoring should be considered to minimize adverse effects.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To define the pharmacokinetics of florfenicol in synovial fluid (SYNF) and serum from central venous (CV) and digital venous (DV) blood samples following regional IV perfusion (RIVP) of the distal portion of the hind limb in cows.

Animals—6 healthy adult cows.

Procedures—In each cow, IV catheters were placed in the dorsal common digital vein (DCDV) and the plantar vein of the lateral digit, and an indwelling catheter was placed in the metatarsophalangeal joint of the left hind limb. A pneumatic tourniquet was applied to the midmetatarsal region. Florfenicol (2.2 mg/kg) was administered into the DCDV. Samples of DV blood, SYNF, and CV (jugular) blood were collected after 0.25, 0.50, and 0.75 hours, and the tourniquet was removed; additional samples were collected at intervals for 24 hours after infusion. Florfenicol analysis was performed via high-performance liquid chromatography.

Results—In DV blood, CV blood, and SYNF, mean ± SD maximum florfenicol concentration was 714.79 ± 301.93 μg/mL, 5.90 ± 1.37 μg/mL, and 39.19 ± 29.42 μg/mL, respectively; area under the concentration versus time curve was 488.14 ± 272.53 h•μg•mL−1, 23.10 ± 6.91 h•μg•mL−1, and 113.82 ± 54.71 h•μg•mL−1, respectively; and half-life was 4.09 ± 1.93 hours, 4.77 ± 0.67 hours, and 3.81 ± 0.81 hours, respectively.

Conclusions and Clinical Relevance—Following RIVP, high florfenicol concentrations were achieved in DV blood and SYNF, whereas the CV blood concentration remained low. In cattle, RIVP of florfenicol may be useful in the treatment of infectious processes involving the distal portion of limbs.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To describe concentration-over-time data for ampicillin and sulbactam in the digital and systemic circulations and synovial fluid (SYN) of cattle following a single injection of ampicillin-sulbactam as a regional IV perfusion (RIVP).

ANIMALS 6 healthy adult nonlactating Jersey-crossbred cows.

PROCEDURES The right hind limb of each cow was aseptically prepared. A tourniquet was applied around the midmetatarsal region, and 1.0 g of ampicillin with 0.5 g of sulbactam in a combined formulation was administered as an RIVP into the dorsal common digital vein (DCDV). Blood samples from the DCDV and jugular vein and SYN samples from the metatarsophalangeal joint of the prepared limb were collected immediately before and at predetermined times for 24 hours after RIVP. One blood sample was obtained from the abaxial proper plantar vein of the lateral digit of the prepared limb 0.25 hours after RIVP. Serum and SYN ampicillin and sulbactam concentrations were determined by high-performance liquid chromatography.

RESULTS Mean ± SD maximum concentration of ampicillin in SYN and serum obtained from the abaxial proper plantar and jugular veins was 1,995 ± 1,011 μg/mL, 5,422 ± 1,953 μg/mL, and 2.5 ± 1.6 μg/mL, respectively. Corresponding serum and SYN concentrations of sulbactam were lower but followed the same pattern over time as those for ampicillin. Synovial fluid ampicillin concentration remained above 8 μg/mL for a mean time of 18.9 hours.

CONCLUSIONS AND CLINICAL RELEVANCE Potentially therapeutic concentrations of ampicillin were achieved in regional serum and SYN samples; SYN concentrations remained at potentially therapeutic values for > 12 hours following RIVP of 1.5 g of ampicillin-sulbactam in the hind limb of healthy cows.

Full access
in American Journal of Veterinary Research