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Intra-articular bupivacaine helps alleviate pain in animals receiving joint surgery, but its use has become controversial as ex vivo studies have illuminated the potential for chondrotoxicity. Such studies typically involve cell cultures incubated in solutions containing high bupivacaine concentrations for long durations. The aim of this study was to measure the actual synovial fluid bupivacaine concentrations after intra-articular injection. Eight healthy beagles with normal stifles and 22 large and giant-breed dogs with stifle osteoarthritis (OA) were treated with a single intra-articular injection of bupivacaine (1 mg/kg) into a stifle. Joint fluid samples were taken from the treated stifle immediately after injection and 30 min after injection and analyzed for bupivacaine concentrations. Immediately after injection, the median bupivacaine concentrations in normal and OA stifles were 3.6 and 2.5 mg/mL, respectively. Thirty minutes after injection, bupivacaine concentrations in normal and OA stifles were 0.4 and 0.6 mg/mL, respectively. These results provide insight into the pharmacokinetics of bupivacaine after injection into a joint. Given its immediate dilution and rapid drop in synovial fluid concentration, bupivacaine is unlikely to damage chondrocytes when administered as a single intra-articular injection. [ABSTRACT FROM AUTHOR]

Wright, H. M., Chen, A. V., Martinez, S. E., Davies, N. M. Pharmacokinetics of oral rufinamide in dogs. J. vet. Pharmacol. Therap. 35, 529-533. The objective of this study was to determine the pharmacokinetic properties and short-term adverse effect profile of single-dose oral rufinamide in healthy dogs. Six healthy adult dogs were included in the study. The pharmacokinetics of rufinamide were calculated following administration of a single mean oral dose of 20.0 mg/kg (range 18.6-20.8 mg/kg). Plasma rufinamide concentrations were determined using high-performance liquid chromatography, and pharmacokinetic data were analyzed using commercial software. No adverse effects were observed. The mean terminal half-life was 9.86 ± 4.77 h. The mean maximum plasma concentration was 19.6 ± 5.8 μg/mL, and the mean time to maximum plasma concentration was 9.33 ± 4.68 h. Mean clearance was 1.45 ± 0.70 L/h. The area under the curve (to infinity) was 411 ± 176 μg·h/mL. Results of this study suggest that rufinamide given orally at 20 mg/kg every 12 h in healthy dogs should result in a plasma concentration and half-life sufficient to achieve the therapeutic level extrapolated from humans without short-term adverse effects. Further investigation into the efficacy and long-term safety of rufinamide in the treatment of canine epilepsy is warranted. [ABSTRACT FROM AUTHOR]

Misoprostol, a prostaglandin E1 analog, is a racemate of four stereoisomers. On administration it rapidly de-esterifies to its active form, misoprostolic acid. Misoprostolic acid is 85% albumin bound and has a half-life of approximately 30 minutes. It is excreted in urine as inactive metabolites. No significant drug interactions have been reported. Besides its gastrointestinal protective and uterotonic activities, misoprostol regulates various immunologic cascades. It inhibits platelet-activating factor and leukocyte adherence, and modulates adhesion molecule expression. It protects against gut irradiation injury, experimental gastric cancer, enteropathy, and constipation. It improves nutrient absorption in cystic fibrosis. Misoprostol has utility in acetaminophen and ethanol hepatotoxicity, hepatitis, and fibrosis. It is effective in asthmatics and aspirin-sensitive asthmatic and allergic patients. It lowers cholesterol and severity of peripheral vascular diseases, prolongs survival of cardiac and kidney transplantation, synergizes cyclosporine, and protects against cyclosporine-induced renal damage. It works against drug-induced renal damage, interstitial cystitis, lupus nephritis, and hepatorenal syndrome. It is useful in periodontal disease and dental repair. Misoprostol enhances glycosoaminoglycan synthesis in cartilage after injury. It prevents ultraviolet-induced cataracts and reduces intraocular pressure in glaucoma and ocular hypertension. It synergizes antiinflammatory and analgesic effects of diclofenac or colchicine and has been administered to treat trigeminal neuralgic pain. It reduces chemotherapy-induced hair loss and recovery time from burn injury, and is effective in treating sepsis, multiple sclerosis, and pancreatitis.

1. Despite the accessibility of the front of the eye, efficient delivery of drug to treat various ocular disorders is a challenge to the formulation scientist. The majority of ophthalmic medications are formulated as eye drops. Due to anatomical constraints, the volume that can be administered is limited to approximately 30 microL. This, together with the efficient clearance system that exists in the front of the eye, makes it difficult to maintain an effective pre-ocular drug concentration for a desired length of time. Various formulation strategies have been used to increase pre-ocular retention of eye drops. The most successful of these has been the inclusion of viscosity enhancing polymers, particularly those able to interact with the mucous layer on the eye surface or those that can undergo a transition from a solution to a gel under the conditions of the pre-ocular area. 2. When the target site is intra-ocular, drug must be absorbed from the pre-ocular region into the eye. The main route for absorption is across the cornea. However, absorption of drug across the cornea is inefficient due to its impermeable nature and small surface area. Thus, the intra-ocular bioavailability of topically administered medications is typically less than 10%. 3. Corneal permeability favours moderately lipophilic compounds. These compounds often have a low aqueous solubility. Problems in ocular drug delivery and formulation are compounded for poorly soluble drugs that must be formulated as suspensions. 4. Reformulation of ophthalmic suspensions as solutions has many advantages. This may be achieved by complexation using cyclodextrins. Solubilization using cyclodextrins can overcome many of the formulation problems. However, it is unclear as to their potential for improving ocular bioavailability, which is seemingly drug dependent and may be influenced by both the physicochemical properties of the drug and the complex formed.

Non-steroidal anti-inflammatory drugs induce damage throughout the entire gastrointestinal tract. Administration of site-specific permeability probes is a non-invasive technique for assessing the functional integrity of the gastrointestinal mucosa. A systematic search tor NSAID-induced permeability studies using MEDLINE and EMBASE, and an analysis of the literature on NSAID-induced gastrointestinal permeability, were carried out. The advantages and disadvantages of the various probes and study protocols are discussed. Identification of the underlying mechanisms of regulatory control of the epithelial tight junction is still needed. A greater appreciation of the pharmacokinetics and distribution of NSAIDs, coupled with gastrointestinal permeability studies, may help delineate the pathogenesis of NSAID-induced gastrointestinal toxicity. Non-invasive tests of gastric, intestinal and colonic permeability have shown promise in both basic research and in clinical practice. While such tests could not replace endoscopy, they may represent clinically useful techniques for identifying patients who would benefit from endoscopy, to assess the response to treatment, and perhaps to predict the clinical course of disease.

This report describes the case of a woman who was admitted to the hospital with severe anemia and refractory rheumatoid arthritis. She had been transfusion dependent for 8 years and was receiving a combination of indomethacin and naproxen. An indium-111 white blood cell scan revealed small bowel inflammation. Salsalate was substituted for her previous nonsteroidal antiinflammatory drugs (NSAIDs), and metronidazole was initiated. This resulted in maintenance of a normal hemoglobin level for at least 1 year after discharge. Small intestine inflammation and bleeding (enteropathy) due to NSAIDs must be considered in the evaluation of anemia in patients with arthritis.