Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site

ObjectiveTo describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration.Study designRandomized crossover experiment; prospective study.AnimalsEleven healthy adult horses between 6 and 20 years of age and weighing 487–592 kg.MethodsIn the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg^?1) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg^?1 SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility.ResultsFollowing IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg^?1 minute^?1 and volume of distribution at steady-state was 3.16 ± 0.65 L kg^?1. Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported.Conclusions and clinical relevanceBuprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.     

Aqueous humor and plasma concentrations of a compounded 0.2% solution of terbinafine following topical ocular administration to normal equine eyes

Objective To determine the transcorneal penetration and systemic absorption of a compounded 0.2% terbinafine solution following repeated topical administration to normal equine eyes. Sample population Six healthy adult horses with normal ocular examinations. Procedures One eye of each horse received 0.2 mL of a compounded 0.2% terbinafine solution every 4 h for seven doses. During the 1 h following administration of the final dose, multiple peripheral blood samples were obtained, and a single aqueous humor (AH) sample was collected at the end of the hour. AH and plasma concentrations of terbinafine were determined using high pressure liquid chromatography (HPLC). Stability of the formulation was assessed with HPLC analysis over a 14‐day time period. Results Terbinafine was not detected in the AH or plasma of any horse at any time point. No signs of ocular irritation or systemic toxicity were noted in any horse at any time point. The solution was stable over 14 days. Conclusion Topical ocular administration of compounded 0.2% terbinafine solution does not result in detectable AH or plasma levels following administration to normal equine eyes, suggesting its use for deep corneal or intraocular fungal infections in equine ophthalmology may be limited.     

Bilateral hydronephrosis secondary to endometriosis managed by endoscopic ureteral stent placement in a captive Guinea baboon (Papio papio)

Spontaneous endometriosis is an estrogen-dependent, progressive and painful disease that affects a variety of nonhuman primates, including several species of baboons (Papio sp.). This case documents multimodal management of severe endometriosis in a captive female baboon within a zoological institution. An 18-yr-old, intact female Guinea baboon (Papio papio) was found to have an enlarged uterus. Fifteen months post ovariohysterctomy, scarring associated with endometrial tissue resulted in ureteral strictures, bilateral hydronephrosis, and azotemia. Cystoscopic placement of bilateral ureteral stents with fluoroscopy was performed and resulted in short-term clinical improvement. The animal's condition declined and euthanasia was elected 4 mo after ureteral stent placement. Severe endometriosis with secondary inflammation resulting in bilateral hydroureter and hydronephrosis, as well as concurrent cystitis, ureteritis, and pyelonephritis were confirmed at necropsy. Despite possible complications, ureteral stents can be considered a useful therapeutic option in patients with ureteral disease.     

Probing mode of action in plant cell cycle by the herbicide endothall, a protein phosphatase inhibitor

The mode of action of endothall, an herbicide which was reported to inhibit plant protein phosphatases 1 (PP1) and 2A (PP2A), was investigated. For initial characterization, a series of bioassays was used for comprehensive physiological profiling of endothall effects which suggested a phytotoxic mode of action similar to mitotic disrupter herbicides. Unlike known microtubule disrupters, endothall did not inhibit soybean tubulin polymerization in vitro. As shown in meristematic corn root tips, endothall distorted the orientation of cell division plane and microtubule spindle structures which led to cell cycle arrest in prometaphase. In tobacco BY-2 cells, malformed spindles together with prometaphase arrest of nuclei and abnormal perinuclear microtubule patterns were detected as early as 4 h of endothall treatment. These effects were also observed after treatment with other protein phosphatase inhibitors, cantharidin and okadaic acid, which phenocopied the mitotic changes described in tonneau1 (ton1) and tonneau2 (ton2) Arabidopsis mutants. These mutants are defective in TONNEAU2 (TON2) protein, a regulatory subunit of PP2A, which governs cell division plane and microtubule orientation. Therefore, PP2A/TON2 phosphatase complex is suggested to be an in planta molecular target of endothall. However, in BY-2 cells, additional effects of endothall, including inhibition of S-phase initiation and DNA synthesis, detected by 5-ethynyl-2′-deoxyuridine (EdU) incorporation, and condensed nuclei arrested in late mitosis were observed which were not reported in Arabidopsiston1 and ton2 mutants. This result indicates that two additional checkpoints in cell cycle were blocked by endothall which are probably not associated with TON2-pathway inhibition. Possibly, inhibition of PP1 and/or other PP2A protein phosphatases are involved in the regulation of these cell cycle phenomena.