Abstract
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.
Highlights
Azithromycin is a macrolide antimicrobial agent of the azalide group which differs structurally from other macrolides by the insertion of a methyl-substituted nitrogen in its lactone ring
A linear regression was performed on the data set, and a regression coefficient (R2) of 0.9988 was obtained for azithromycin
Azithromycin was detected with potassium dihydrogen phosphate buffer and methanol (20:80) at a flow rate of 1.7 ml/min and detector wavelength of 215 nm
Summary
Azithromycin is a macrolide antimicrobial agent of the azalide group which differs structurally from other macrolides by the insertion of a methyl-substituted nitrogen in its lactone ring. This structural modification significantly increased its potency against gram-negative bacteria when compared to erythromycin, with retention of activity against grampositive bacteria [1]. Tolfenamic acid is a non-steroidal anti-inflammatory drug (NSAID) of the fenamate group. It is used extensively in humans, dog, cat, calf, and pig medicine for its anti-inflammatory, analgesic, and antipyretic properties. Tolfenamic acid and azithromycin are licensed for the therapy of calf respiratory disease
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