Toltrazuril sulfone (Ponazuril) is a triazine-based anti-protozoal agent with highly specific actions against apicomplexan group of organisms, which are undergoing intensive investigation. Toltrazuril sulfone may have clinical application in the treatment of Neospora. caninum and other protozoal infections in cattle. To evaluate absorption, distribution, and elimination characteristics of toltrazuril sulfone in cattle, a sensitive validated quantitative high-pressure liquid chromatography method for toltrazuril sulfone in bovine biological fluids was developed. After a single oral dose of toltrazuril sulfone at 5 mg/kg (as 150 mg/g of Marquis; Bayer HealthCare, Shawnee Mission, KS, USA), samples from six cows showed good plasma concentrations of toltrazuril sulfone, which peaked at 4821 ng/mL +/- 916 (SD) at 48 h postadministration. Thereafter, plasma concentration declined to 1950 ng/mL +/- 184 (SD) at 192 h after administration with an average plasma elimination half-life of approximately 58 h. Following oral dose of toltrazuril sulfone, the observed peak plasma concentrations were in relatively close agreement ranging from the lowest 3925 ng/mL to the highest of 6285 ng/mL with the mean peak plasma concentration being 4821 ng/mL. This study shows that toltrazuril sulfone is relatively well absorbed after oral dose in cattle. These results are therefore entirely consistent with and support the reported clinical efficacy of toltrazuril sulfone in the treatment of experimentally induced clinical cases of N. caninum and other protozoal-mediated bovine diseases.

DNA Alkylation is thought to be the reason for the efficacy of lomustine while carbamylation has been implicated as the cause for the side effects seen with lomustine treatment such as hepatotoxicity. In the alkylation study we show that lomustine and its metabolites form similar levels of the DNA adducts N7 hydroxyethylguanine and O6 hydroxyethyldeoxyguanosine. In terms of carbamylation, lomustine showed greater extent of carbamylation in the canine hepatocytes and lymphoma cell lines. The DNA repair enzyme O6 methylguanine DNA methyltransferase (MGMT) causes resistance of tumor cells to bifunctional nitrosourea, like lomustine. There is no data available regarding MGMT expression/activity in canine cells or tissues. Our study shows that there is low MGMT activity in the canine lymphoid cell line 17–71 while the GL-1 cells did not show any detectable enzyme activity or mRNA expression. The MGMT enzyme activity measured in canine hepatocytes is about 250–350 fmol/mg protein as compared to about 90 fmol/mg protein in 17–71 cells. We also show that MGMT mRNA expression in 17–71 cells and canine hepatocytes positively correlates with its enzyme activity in these cells.

This study evaluated the safety (absence of toxicity) of StemEnhance™, an extract of the blue-green alga Aphanizomenon flos-aquae that is used as a health supplement. Groups of 12 rats of each sex were given either 5% glycerin in water (control) or 600 mg/kg of StemEnhance prepared in 5% glycerin in water for 2 weeks by oral gavage followed by 2 weeks of observation. The administration of StemEnhance had no effect on behavior, food and water intake, growth, or survival. Values at the end of dosing and observation periods did not reveal differences between treated and control groups for hematology and clinical chemistry. There were no significant differences in the gross and histopathology of the reproductive organs in either males or females. Sperm motility parameters were similar for control and treated males. Our results show that StemEnhance at doses ∼20 times the maximum label-recommended daily dose did not produce adverse effects in Wistar rats after subacute treatment.

In veterinary medicine, lomustine has been successfull used primarily for the treatment of resistant lymphoma and also for the treatment of mast cell tumors, intracranial meningioma, epitheliotropic lymphoma, and histiocytic sarcoma in dogs either alone or in combination with other chemotherapeutic agents. Even though lomustine is commonly used in dogs primarily for the treatment of resistant lymphoma, there is no pharmacokinetics information available regarding this compound in dogs. In the present study, we developed and validated a simple high-performance liquid chromatography (HPLC) method with a one-step liquid-liquid extraction procedure to detect and quantify lomustine and its two monohydroxylated metabolites (trans- and cis-4'-hydroxylomustine) in canine plasma for future pharmacokinetic studies. The HPLC-diode-array detection method reported here readily detects lomustine, cis-4'-hydroxylomustine, and trans-4'-hydroxylomustine in canine plasma with a limit of detection of lomustine, cis-4'-hydroxylomustine, and trans-4'-hydroxylomustine in plasma of about 10 ng/120 microL, 5 ng/120 microL, and 5 ng/120 microL, respectively. The mean extraction efficiency values for lomustine, cis-4'-hydroxylomustine, and trans-4'-hydroxylomustine were 73%, 90%, and 89%, respectively, from canine plasma samples on HPLC. The present study also provides stability information about lomustine and its two monohydroxylated metabolites in canine plasma and methanol solution stored at various conditions.