STUDIES ON EFFECT OF KETOPROFEN, FEBRILE CONDITION AND BIOENHANCER TRIKATU AND ITS CONSTITUENTS ON PHARMACOKINETICS OF LEVOFLOXACIN AND SAFETY OF LEVOFLOXACIN IN GOATS
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Date
2012
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AAU, Anand
Abstract
Levofloxacin is a novel third generation fluoroquinolone with broad spectrum antibacterial activity. Use of non-steroidal anti-inflammatory drugs (NSAIDs) are frequently recommended with antibacterials for the treatment of various bacterial infections accompanied by fever and other inflammatory conditions in animals. Ketoprofen (KTP) is an aryl propionic acid derivative, non-selective COX inhibitor NSAID having anti-inflammatory, analgesic and antipyretic properties. In veterinary practice, ketoprofen is used to lower body temperature in animals having fever, to relieve bacteremia and pain in all animals. Pharmacokinetics of an antibacterial drug may change when administered with anti-inflammatory drug or in febrile animals. Despite the great potential for clinical use of levofloxacin, the data on its pharmacokinetics and safety profile in goat are scarce. Ancient and recent scientific literature cited reference of bioenhancer like Trikatu (Piperine) application to increase bioavailability of drug and nutrients. Moreover, it is well known in ruminant animals that oral bioavailability of drug is low as compared to monogastric animals. Looking to this, present study was conceptualized to determine the effect of intramuscularly administered ketoprofen (3 mg/kg body weight) and febrile condition (lipopolysaccharide (LPS) induced) on pharmacokinetics of levofloxacin following intravenous, subcutaneous and oral administration (4 mg/kg body weight) in goats and safety of daily intravenous and subcutaneous administration of levofloxacin alone (4 mg/kg body weight) and in combination with intramuscular administration of ketoprofen (4 mg/kg body weight) for five days in goats by monitoring hematological and blood biochemical profiles. Moreover, effect of bioenhancer Trikatu and its constituents (Piperine equivalent to 20 mg/kg body weight) on pharmacokinetics of levofloxacin following oral administration (4 mg/kg body weight) in goats was evaluated. In addition to this bioenhancing effect methanolic extract of Trikatu (30 mg/kg body weight), Piper longum (30 mg/kg body weight), Piper nigrum (30 mg/kg body weight) and Zingiber officinale (30 mg/kg body weight) was evaluated following oral administration of levofloxacin (4 mg/kg body weight). The high performance liquid chromatography apparatus comprising quaternary gradient delivery pump, UV detector and reverse phase C18 column at room temperature. The mobile phase consisted of a mixture of 1% triethylamine in water and acetonitrile (85:15 v/v) adjusted to pH 3.0 with ortho-phosphoric acid and pumped into column at a flow rate of 1.5 mL/min at ambient temperature. The HPLC data integration was performed using software Clarity (Version 2.4.0.190). Following intravenous administration of levofloxacin in normal, ketoprofen treated, and febrile goats, the plasma drug concentration > 0.015 µg/ml was detected up to 18 h. Following intravenous administration of levofloxacin in ketoprofen-treated goats, no significant changes in pharmacokinetic parameters were observed compared to pharmacokinetic parameters of levofloxacin in normal goats. Following intravenous administration of ievofloxacin in febrile goats, values of AUC (13.48 ± 0.48 µg.h/mL) and AUMC (40.01 ± 2.66 µg.h2mL) were significantly higher and Vdarea (1.05 ± 0.04 L/kg) was significantly lower than the values obtained following levofloxacin administration in normal goats.
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VETERINARY PHARMACOLOGY & TOXICOLOGY, A STUDY