administration in local goat (Capra hircus) of Assam

Aim: The aim of the present study was to determine the meloxicam concentrations in the plasma of goats at different time intervals after its administration by IV route and data were used to determine the different pharmacokinetic parameters and the bioavailability of meloxicam in goats. 
 
Materials and Methods: The present study was conducted on 12 to 18 months old, five adult male local goats (Capra hircus) of Assam, with body weight ranging between 10 to 18 kg. All goats were clinically sound and healthy and reared at Goat Research station, Burnihat, Assam. A single dose of meloxicam was administered intravenously into the jugular vein of goats at the rate of 1 mg/kg body weight. Blood samples were analyzed with the help of high performance liquid chromatography (HPLC) system. 
 
Results:After single intravenous administration of meloxicam at the dose rate of 1mg/kg, the mean peak plasma level of the drug was 6.538±0.1189 μg/ml at 2 min. The mean elimination half life (t ) and mean distribution half life (t ) were 1/2â 1/2a 484.5±85.1202 min and 28.68±1.4206 min respectively. The mean values of AUC and AUMC were 2635.272±94.2389 μg.min/ml and 1620332±92456.46 μg.min2/ml respectively. The mean values of volume of distribution (Vd) and mean residence time (MRT) were 0.276±0.0103 L/kg and 612.948±14.5771 min respectively. 
 
Conclusion: After calculating various pharmacokinetic determinants, dosage regimens were computed for meloxicam in goats, based on minimum effective therapeutic plasma concentration of 0.7 μg/ml.To maintain the minimum effective concentration of 0.7 μg/ml in plasma for 25 hours following iv administration of meloxicam,an initial loading dose of 1.1 mg/kg body weight followed by a maintenance dose of 1mg/kg body weight/day is recommended.


Introduction
Meloxicam is used in cattle for the treatment of acute respiratory infection in combination with Meloxicam (MEL) (4-hydroxy-2-methyl-N- (5-appropriate antibiotic, diarrhea with oral rehydration, methyl-2-thiazolyl)-2H-1,2-benzothiazine-3acute mastitis along with antibiotic therapy.In swine, carboxamide-1,1-dioxide) is a non-steroidal anti-inflameloxicam is used in non-infectious locomotor disorders mmatory drug (NSAID) of the oxicam class belonging to reduce lameness and inflammation and for adjunctive to the group of enolic acids, having a molecular formula therapy in septicemia and toxemia (mastitis-metritis-C H N O S , molecular weight 351.4,melting point 14 1 3 4 2 agalactia syndrome) with appropriate antibiotic 254ºd, used widely in both human and veterinary therapy.In horses, it is indicated for the reduction of medicine [1].The importance of NSAIDS especially inflammation and pain associated with chronic meloxicam has been proved beyond any doubt.musculoskeletal disorders.The intended indications Meloxicam is a novel NSAID that has effectively for goats are adjunctive therapy of acute mastitis and replaced the old pain killers particularly diclofenac acute respiratory infection with appropriate antibiotic sodium which has high toxicity [1].Besides this therapy.meloxicam has high anti-inflammatory efficacy with Meloxicam has been shown to have a high antilow ulcerogenic potency and shows less gastric arthritic activity, anti-inflammatory activity and at the irritation and local tissue irritation in comparison to same time it causes less gastric and local tissue other NSAIDS.It is a broad spectrum drugs that covers irritation as compared to NSAIDs available prior to its a number of diseases especially canine osteoarthritis develop-ment [4,5].It was used in the management of [2,3].Hence its indiscriminate use should be avoided rheumatoid arthritis, osteoarthritis and ankylosing and appropriate rational therapy should be followed spondylitis by relieving pain and reducing swelling and according to proper dose schedule.This has made the inflammation [6], with higher therapeutic index than detailed pharmacokinetic study of the drug compulsory.
grade Acetonitrile.(EMERCK), HPLC grade Water.There is lot of interspecies variation in the (EMERCK).pharmacokinetic profile of meloxicam and hence its disposition kinetics in one species cannot be Estimation of meloxicam: Each animal was weighed extrapolated for use in other species.Goat is an on a balance to evaluate the dose .A single dose of meloxicam was administered intravenously into the important meat animal and is reared extensively in the jugular vein of goats at the rate of 1 mg/kg body state of Assam as well as all other Indian states.Despite weight.Blood samples (3-4 ml) were collected by the tremendous therapeutic potential of meloxicam in jugular vein puncture with the help of a 5ml syringe, small ruminants, not much information is available on into vacutainer heparinised tubes from each animal the pharmacokinetics of meloxicam in sheep and goat.
prior and after both drug administration.The time of Hence, the present study of determination of blood collection after IV administration was 2,5, 10, pharmacokinetics of meloxicam in local goat of Assam 15,30,45,60,120,240,360,480,720,1440 and 2880 min was undertaken with the following objectives: respectively.The plasma was extracted after a) Determination of plasma level of meloxicam centrifugation of blood samples at 3500 rpm for 10 following i.v administration in local goat of Assam.
min at room temperature.Extracted plasma was stored b) Determining the kinetic profile of meloxicam in 1.5ml capped micro-centrifuge tubes in a refrigefollowing i.v administration in local goat of Assam.
rator at -5ºc, until analysed.Analysis of the samples c) Determining the dose and dosage frequency of were carried out within 3-4 days of collection of plasma.meloxicam for local goat of Assam.
For the quantitative estimation of meloxicam in

Materials and Methods
the plasma samples of goat, HPLC method by Baert and De Backer [25] was followed with slight Experimental animals: The present study was conducted modification.Plasma analysis was performed on a on 12 to 18 months old, five adult male local goats High Performance Liquid Chromatography (HPLC).(Capra hircus) of Assam, with body weight ranging The mobile phase used for the HPLC system consisted between 10 to 18 kg.All goats were clinically sound of a mixture of 65% water : acetic acid (99:1, v/v) and and healthy and reared at Goat Research station, 35 % acetonitrile with a flow rate of 0.8 ml/min.Detection Burnihat, Assam.
of meloxicam was done at 355 nm wavelength with a Ethical approval: All the ethical principles were column oven temperature 35 ºc.The retention time of followed during the course of research and the meloxicam was about 6.65 min.experiments were carried out in accordance with the Chemical analysis of meloxicam: The previously collected guidelines laid down by the International Animal plasma samples were used for meloxicam estimation.Ethics Committee (IAEC) and in accordance with the 0.5 ml of Acetonitrile was added to 0.5 ml of plasma local laws and regulations.The animals were housed samples in the ratio of 1:1.This was mixed thoroughly in animal shed with wooden floor and were provided with the help of a Vortex Mixer for 1-2 min and then with concentrate, green fodder and dry grass.Water centrifuged for 15 min at 6000 rpm.The clear was provided ad libtum.Deworming was done 15 days supernatant so obtained was transferred to a clean tube.prior to the start of the experiment with the help of Again 0.5 ml of the supernatant was added to 0.5 ml of albendazole given @ 1ml/kg.The average temperature HPLC Grade water and mixed well.Then the aliquot of the environment in and around the goat research was filtered through 0.22 µm nylon filter paper.Finally station was around 30ºc during the course of experiment.20 µl of the aliquot was injected into HPLC system for Instruments required: High performance liquid the analysis.Preparation of standard curve: Blank plasma collected meloxicam concen-trations in plasma at different time before the injection of the drug into the goats was intervals, various pharmacokinetic parameters have spiked with the standard of meloxicam at a been determined.The plasma levels of meloxicam concentration of 0.5,1.0,1.75,2.5,5.0,7.5,10.0,15.0 and following single intravenous administration at the 20.0 µg/ml of plasma.These plasma standards were dose rate of 1 mg/kg at different time intervals in goats prepared and extracted as described above for the have been presented in Table - The mean peak plasma level of meloxicam was from log plasma drug concentration versus time profile 6.538±0.1189µg/ml at 2 min, which declined rapidly by "two compartment open model" as described by to 3.964±0.0793µg/ml at 60 min of time, thereafter the Gibaldi [26].For each parameter the mean and its SE decline was steady and the lowest concentration of were obtained from the parameters estimates of five about 0.028±0.0058µg/ml was observed at 2880 min.

animals. Statistical analysis was done following
With the help of plasma drug concentrations the standard statistical method [27].
different pharmacokinetic parameters of Meloxicam

Results
were calculated in goat and shown in the   tively.The mean values of volume of distribution (Vd) MRT is the average or mean time required for a and mean residence time (MRT) were 0.276±0.0102drug molecule to travel or traverse throughout the body L/kg and 612.948±14.5771min respectively.The and thus reflects the time associated with absorption, minimum effective therapeutic concentration or minimum distribution, metabolism and elimination.This is very effective plasma concentration of meloxicam is about useful in calculating the dosing interval of a drug in a 0.7 µg/ml.This amount was detectable up to 1400 min particular species.MRT obtained in the present study following single intravenous administration.

Discussion
This again reflects that the drug is eliminated at a faster The present study, the plasma level of meloxicam rate in goats than in sheep and cattle which is very was 6.538±0.1189µg/ml at 2 min, which declined consistent with other observations of the study.The rapidly to 3.964±0.0793µg/ml at 60 min of time, value of volume of distribution (Vd) in the present study thereafter the decline was steady and the lowest was observed 0.276±0.156L/kg which was more than concentration of 0.028±0.0058µg/ml was observed at cattle (0.171 L/kg) [10,11].This indicates that the about 2880 min.Similar patterns of plasma levels were meloxicam is well distributed in goats than in cattle also observed in other animals [12].The value of when given intravenously.distribution half life (t ) was 28.68±1.4206min.

Conclusion
Similar values of distribution half life for meloxicam have been observed in horses (24 min) and sheep ( 26Results obtained in goat revealed that the data min ) respectively [12,16].The value of short half life followed the first order rate kinetics like many other indicates that the drug is distributed quite rapidly in NSAIDS and that it could be best fitted to a two goats.
compartmental open model.The minimum effective The value of mean elimination half life (t ) was therapeutic concentration or minimum effective dose should be reduced to avoid the drug accumulation.min) and turkeys (60 min) [25].The comparatively After calculating various pharmacokinetic determismaller value of t observed in the present study in 1/2â nants, dosage regimens were computed for meloxicam goats implies that the drug is eliminated at faster rate in goats,based on minimum effective therapeutic as compared to sheep and horses.This is supported by plasma concentration of 0.7 µg/ml.To maintain this the fact that goats possess higher drug metabolizing minimum effective concentration of 0.7 µg/ml in activities in liver and other organs and have been shown plasma for 25 hours following iv administration of to eliminate sulphadimidine, antipyrine, ampicillin and meloxicam,an initial loading dose of 1.1mg/kg body isometamidium at a significantly faster rate than sheep weight followed by a maintenance dose of 1mg/kg [28].
body weight/day is recommended.The drug was The area under curve is an important pharmacodistributed in the body very quickly with a mean kinetic determinant.It forms the basis for the calculation distribution half life (t ) of 28.68±1.4206min.The of other pharmacokinetic parameters such as MRT, Vd, 1/2á F etc. The value of AUC obtained in the present study mean value of volume of distribution (Vd) after iv of meloxicam was 2635.272±94.2389µg.min/ml.This administration was 0.276±0.0103L/kg.This again is lower than that of cattle (4940.4µg.min/ml) [10,11].
indicates that the distribution of meloxicam was faster This implies that the drug is eliminated at a faster rate and better after IV administration The drug was from the body of goats in comparison to cattle.eliminated from the body somewhat quickly with a doi:10.5455/vetworld.2013.516-520

Figure- 1 .Figure- 2 .
Figure-1.Plasma concentration of Meloxicam in HPLC data system after IV administration

Table - 1
. Plasma concentrations (µg/ml) of Meloxicam in goats after intravenous administration at the dose rate of 1 mg/kg body weight.*(n=5)

Table - 2
. Pharmacokinetics of Meloxicam after single intravenous administration at the dose rate of 1 mg/kg body weight in goat.