Effect of medetomidine on tear flow measured by Schirmer tear test I in normal pigs.

Medetomidine, an α2-adrenoceptor agonist, was reported to decrease tear flow in some species. However, there are no reports about the effect of medetomidine on tear flow in pigs. The purpose of this study was to elucidate it. The study was performed in 10 clinically normal female Landrace pigs aged 3 months. Tear flow was measured by the Schirmer tear test (STT) I before (baseline) and 15 and 30 min after intramuscular administration of 80 µg/kg medetomidine. Compared to the STT I value at baseline, the value decreased significantly at 30 min after administration in both the left and right eyes. In pigs treated with medetomidine, an artificial tear solution or ophthalmic gel should be applied to protect the ocular surface.

Sedative and physiological effects of brimonidine tartrate ophthalmic solution in healthy cats.

OBJECTIVE: To determine the effects of brimonidine tartrate ophthalmic solution on sedation, heart rate (HR), respiratory frequency (fR), rectal temperature (RT) and noninvasive mean arterial pressure (MAP) in healthy cats. STUDY DESIGN: Randomized, blinded crossover study, with 1 week washout between treatments. ANIMALS: Six healthy purpose-bred cats. METHODS: Brimonidine tartrate ophthalmic solution 0.1% (one or two drops; 58.6 ± 3.3 µg per drop) or a control solution (artificial tear solution) was administered to six healthy cats. Behavioural observations and measurements of HR, fR, RT and MAP were recorded before and at 30, 60, 90, 120, 180, 240, 300 and 360 minutes after topical administration. Behavioural scores were analysed using Friedman's test for repeated measures to evaluate the time effect in each treatment and treatment effect at each time point. Physiological variables (HR, fR, RT and MAP) were analysed using two-way analysis of variance for repeated measures to evaluate the time and treatment effects. The level of significance was set at p < 0.05. RESULTS: Dose-dependent behavioural and physiological responses were noted. A dose of two drops of brimonidine resulted in sedation in the cats and decreased HR and MAP. Significant sedative effects occurred between 30 and 120 minutes and for physiological responses up to 360 minutes. The most frequent adverse reaction was vomiting, occurring within 40 minutes in all six cats administered two drops and five of the six cats administered one drop of brimonidine. CONCLUSIONS AND CLINICAL RELEVANCE: The results demonstrated that ocular administration of brimonidine 0.1% ophthalmic solution induced sedation in cats and some cardiovascular effects usually associated with α2-adrenoceptor agonists. Further studies should be performed to determine clinical applications for this agent in cats.

Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.

A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration.

The bisphosphonate incadronate inhibits intraperitoneal dissemination in an in vivo pancreatic cancer model.

Pancreatic cancer is characterized by intraperitoneal dissemination and often by large volumes of ascites. Aminobisphosphonates exhibit potent antitumor effects and are currently being tested against human solid tumors. Several aminobisphosphonates inhibit cancer cell migration by preventing the activation of Rho through inhibition of the mevalonate pathway. We evaluated the ability of an aminobisphosphonate, incadronate, to inhibit the growth of disseminated pancreatic cancer in vivo. We established an in vivo pancreatic cancer model with i.p. carcinomatosis in nude mice. Incadronate administration started from the day of tumor inoculation, and reduced tumor burden and ascites accumulation. Further, we evaluated the effect of incadronate on the inhibition of pancreatic cancer cell proliferation, migration and invasion in vitro. Incadronate induced growth inhibition and apoptotic death of pancreatic cancer cells. It also inhibited migration presumably by preventing the activation of Rho by lysophosphatidic acid. Thus, the in vivo antitumor effect may result from the inhibition of cancer cell proliferation and migration. The potent effects of incadronate in reducing tumor burden and ascites suggest that it will be of value in regimens for the treatment of pancreatic cancer.