The pharmacokinetics, bioavailability, and tolerability of tolfenamic acid (TA) were determined after treating sheep with TA via different routes and doses. This crossover study was carried out with a washout period of 15 days. In the study, 16 clinically healthy sheep were randomly assigned to two equal groups. In the first group (n = 8), animals received TA by intravenous (IV), intramuscular (IM), subcutaneous (SC), or oral (OR) routes at 2 mg/kg. In the second group (n = 8), TA was administered intravenously to each sheep at 2, 4, 8, and 16 mg/kg. Plasma samples were analyzed with a high-performance liquid chromatography assay. Noncompartmental pharmacokinetic analyses were used to evaluate the data. The area under the concentration-time curves (AUC ), elimination half-life (t ), and the mean residence time (MRT) significantly differed among the administration routes at 2 mg/kg of TA. Following IM, SC, and OR administrations, TA demonstrated different peak concentrations (C ) and time to reach C (T ), with a bioavailability of 163%, 127%, and 107%, respectively. The dose-normalized AUC revealed a significant difference among the dose groups; however, the relationship between dose and AUC was linear. Both t and MRT increased depending on the dose. Although the total clearance (Cl ) decreased depending on dose, the volume of distribution at steady-state (V ) increased. Tolfenamic acid indicated a long half-life and high bioavailability following IM, SC, and OR administrations at 2 mg/kg. TA exhibited linear kinetics and was well tolerated by the animals, except at 16 mg/kg. Thus, TA may be used in different routes and doses (≤8 mg/kg) in sheep; however, further studies are needed to determine the clinical efficacy of TA during the inflammatory and painful conditions and the pharmacokinetics and safety of repeated administration in sheep.

Increased levels of BNP are more likely related to the severity of disease in non-alcoholic cirrhotic patients. The advanced cirrhosis is associated with more advanced cardiac dysfunction and BNP has prognostic value in progression of cirrhosis.

Surfactant deficiency, poor development of the lung structure and fibrosis as a result of inflammation are thought to play an important role in the development of respiratory distress syndrome in premature calves. Nebulised steroid (fluticasone), bronchodilator (salbutamol) and diuretics (furosemide) can be used in combination alongside standard treatment procedures for premature calves, and might improve viability as observed in infants, foals and horses with pulmonary disorders. Twenty-five premature calves with respiratory distress syndrome were used in this study. Oxygen and supportive treatment were administered to all groups. The first group was used as a control group (Group 1). The nebulised drug combinations were as follows: Group 2: fluticasone + salbutamol, Group 3: salbutamol + furosemide, Group 4: fluticasone + furosemide and Group 5: fluticasone + salbutamol + furosemide. During the 72-h time period of the study, fluticasone (15 µg/kg/12 h), salbutamol (0.025 mg/kg/6 h) and furosemide (1 mg/kg/12h) were applied for 5 min. Arterial blood samples were collected from the auricular artery at 0 h and at 1, 24, 48 and 72 h for blood gas analysis. Significant (P < 0.05) increases in arterial partial oxygen, oxygen saturation and peripheral oxygen saturation and decreases in arterial partial carbon dioxide, lactate and respiration rate were observed in all the nebulised treatment groups, while a statistical difference was observed only for arterial partial carbon dioxide in control group. When comparing the treated groups with the control, it may be concluded that nebulised drugs are highly effective in the therapy of premature calves with respiratory distress syndrome, while the different nebulised groups exhibited similar efficacies.

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