Influence of Pyrexia on Pharmacokinetics of Azithromycin and Its Interaction With Tolfenamic Acid in Goats

Azithromycin is a macrolide antimicrobial agent of the azalide group with a broad spectrum of activity against gram-negative and gram-positive bacterial organisms. Tolfenamic acid is a non-steroidal anti-inflammatory drug of the fenamate group, which is used extensively in humans and animals due to its anti-inflammatory, analgesic, and antipyretic properties. There is dearth of literature on any type of drug interaction between azithromycin and tolfenamic acid in any species, including human beings and alteration of its pharmacokinetics by fever. Therefore, the objective of this study was to investigate the alteration of disposition kinetics of azithromycin alone and in the presence of tolfenamic acid in Malabari goats by fever, following an intravenous administration at a dose rate of 20 mg/kg body weight. Blood samples collected from both afebrile and febrile goats at predetermined time intervals after the administration of azithromycin alone and then in combination with tolfenamic acid (2 mg/kg, intravenously), respectively, were analyzed using high-performance liquid chromatography. Non-compartmental analysis was used to determine the peak blood concentration (Cmax), time-to-peak plasma concentration (Tmax), half-life (t1/2λz), area under the curve (AUC 0−t, AUC 0−inf), area under the first moment curve (AUMC 0−inf), mean residence time (MRT0−inf), apparent volume of distribution at steady state (Vss), and the total body clearance of drug from the blood (Cl). In febrile animals, significant differences were noted in the values of Cmax, Cl, and Vss. Thus, azithromycin disappears into an additional compartment in febrile goats, which may be due to its extended cellular penetration into the inflammatory cells, resulting in anti-inflammatory activity. Tolfenamic acid significantly altered the pharmacokinetics of azithromycin in both normal and febrile animals. Tolfenamic acid, being a better anti-inflammatory agent, suppresses the inflammatory mediators, reducing the possibility of increased utilization of azithromycin in febrile condition.

Research on 3D Elastoplastic Seismic Performance of Reinforced Concrete Special-shaped Column Frame

The special-shaped column structure system has more advantages than the rectangular column system in terms of architectural design and actual use. As a relatively new structural form, the concrete special-shaped column structure has not accumulated enough engineering practical experience. In this study, the rotation-moment curve of the plastic hinge of special-shaped column frame element was defined, the coupled PMM hinge applied to the frame element was studied, and the yield surface of the hinge was drawn. On this basis, an elastoplastic pushover analysis was conducted on a 12-storey special-shaped column frame model, its failure under different earthquakes was simulated, and its seismic performance was studied. The work of this article can provide reference for the engineering application of special-shaped column frame structure.

Dexmedetomidine and ketamine simultaneous administration in tigers (Panthera tigris): pharmacokinetics and clinical effects

BackgroundThe study determines the pharmacokinetic profiles of dexmedetomidine (DEX), ketamine (KET) and its active metabolite, norketamine (NORKET), after simultaneous administration. Moreover, the study evaluates the sedative effects of this protocol, its influence on the main physiological variables and the occurrence of adverse effects.MethodsEighteen captive tigers were initially administered with a mixture of DEX (10 µg/kg) and KET (2 mg/kg) by remote intramuscular injection. In case of individual and specific needs, the protocol was modified and tigers could receive general anaesthesia, propofol or additional doses of DEX and KET.ResultsBased on the immobilisation protocol, nine animals were assigned to the standard protocol group and the other nine to the non-standard protocol group. Higher area under the first moment curve (AUMC0-last) and longer mean residence time (MRT0-last) (P<0.05) were observed in the non-standard protocol group for DEX, KET and NORKET, and higher area under the concentration-time curve from administration to the last measurable concentration (AUC0-last) only for KET. The KET metabolisation rate was similar (P=0.296) between groups. No differences between groups were detected in terms of stages of sedation and recoveries. All physiological variables remained within normality ranges during the whole observation period. During the hospitalisation period, no severe adverse reactions and signs of resedation were observed.ConclusionThe simultaneous administration of 10 µg/kg of DEX and 2 mg/kg of KET can be considered an effective protocol for chemical immobilisation of captive tigers, along with dosage adjusments or when other drugs are needed.