Many drugs of same generic are marketed by more than one pharmaceutical maker in market. Many surveies have shown that method of fabrication and composing of active and inactive stuff in the preparation can act upon the pharmacokinetics of drug. In last decennary, the figure of pharmaceutical industries has increased and these are besides fabricating the same drugs which are research merchandise of a transnational company.
For illustration, montelukast ‘s more than 25 trade names are available in Pakistan but it is difficult to state that every trade name nowadays in market have the same efficaciousness. So, the bioequivalence survey is of much of import to guarantee that this drug can bring forth coveted effects.Bioequivalence can be defined as, “ two pharmaceutical merchandises are bioequivalent if they are pharmaceutically tantamount and their bioavailabilities ( rate and extent of handiness ) after disposal in the same grinder dosage are similar to such a grade that their effects, with regard to both efficaciousness and safety, can be expected to be basically the same.
Pharmaceutical equality implies the same sum of the same active substance ( s ) , in the same dose signifier, for the same path of disposal and run intoing the same or comparable criterions. ” ( Birkett, 2003 )It can besides be defined as, “ the absence of a important difference in the rate and extent to which the active ingredient or active mediety in pharmaceutical equivalents or pharmaceutical options becomes available at the site of drug action when administered at the same grinder dosage under similar conditions in an suitably designed survey. ” ( United provinces Food and Drug Administration, 2003.
; www.fda.gov ) .The intent of bioequivalence surveies is to show the bioequivalence between two generic drug merchandises and the corresponding mention drug. Pharmaceutical equality is determined and this bioequivalence allows a regulative decision that these drugs are besides curative equivalent. Bioequivalence surveies besides evaluate the systemic exposure profile of a trial drug merchandise in comparing to a mention drug merchandise ( Huixiao et al.
2009 ) . Bioequivalence besides plays a really of import function in the period of drug development. It is non merely for the survey of a new drug but besides for their generic equivalents.
These surveies have besides importance in the postapproval period as certain fabrication alterations can impact the bioequivalence of drug. Besides the safety and effcicay of drug on the footing of systemic exposure is measured ( Mei-Ling et al. , 2001 ) .Bioequivalence survey besides help to set the doses in a fixed dose combination ( FDC ) as recommended by WHO to increase patient conformity. Drugs in fixed dose combination can be compared to their separate dose signifier and besides drug interactions can be studied. ( Agrawal et al. 2001 ) . Bioequivalence surveies besides help to measure the curative comparing of tested drugs ( pharmaceutical equivalents or pharmaceutical options ) .
The importance of bioequivalence surveies is increasing twenty-four hours by twenty-four hours due to the big handiness generic trade names in market and their ingestions. ( Vetchy et al. , 2007 ) . Metabolic profiles can alter the pharmacokinetics of the drugs, so bioequivalence surveies besides help in survey and comparing of metamorphosis of drug in different population.
( Srinivas, N.R. 2009 ) .
In bioequivalence survey based on pharmacokinetic parametric quantities and pharmacodynamics parameters.Pharmacokinetic is “ the survey of the action of drugs within the organic structure, which can, in many respects, be envisioned more accurately as the actions of the organic structure on an administered drug. It includes surveies of the mechanisms of drug soaking up, distribution, metamorphosis, and elimination ; oncoming of action ; continuance of consequence ; biotransformation ; and effects and paths of elimination of the metabolites of the drug. ” ( Mosby ‘s medical lexicon, 2009 ) . So clinical pharmacokinetics surveies are really of importIn pharmacokinetic/pharmacodynamic survey, drug concentration & A ; metabolic profiles are measured in voluntaries for the rating of efficaciousness and safety.
These pharmacokinetic surveies are performed to analyze soaking up, distribution, metamorphosis and elimination of drugs in healthy voluntaries and/or patients. It helps in the accommodation of dose harmonizing to disease and genotype of drug metabolising enzyme & A ; on footing of pharmacokinetic drug interactions. Therefore, it is besides of import to measure single ( healthy/patients ) pharmacokinetic parametric quantities to minimise inauspicious drug effects and increase efficaciousness of the drug ( Clinical pharmacokinetics surveies ; www.nihs.go.jp ) .
Montelukast Na is unwritten leukotriene receptor adversary ( LTRA ) . It blocks portion of the inflammatory procedure associated with an asthma onslaught and therefore helps to cut down swelling or bottleneck of air passages. It is besides used for the intervention of seasonal allergic reactions. ( Lipkovitz et al 2001 ) . It is used as an add-on therapy in the long term direction of asthma when intervention with inhaled beta receptor stimulations and corticoids.Peak plasma concentrations of montelukast are achieved in 3 to 4 hours after unwritten doses.
The average unwritten bioavailability is 64 % . Montelukast is more than 99 % edge to plasma proteins. It is extensively metabolized in the liver by cytochrome P450 isoenzymes CYP3A4, CYP2A6, and CYP2C9, and is excreted chiefly inthe fecal matters via the gall ( Martindale, the complete drug refrence ) .Different gender difference surveies were done but it was concluded that it did non impact the pharmacokinetics of montelukast. ( Haiyng et al. 1996 ) . It is category B drug and is safe to give pregnant adult female.
If montelukast is given with Phenobarbital, serum concentration of montelukast will diminish, so dose accommodation is necessary if administered with Phenobarbital ( Holland et al.1998 ) .
Aim OF THE STUDY:
The chief aim of the survey is to: -The intent of this survey is measure the bioequivalence of individual dosage of 10mg montelukast tablet of a locally manufactured locally as trial preparation ( T 10 milligram ) with a mention preparation R ( SingularA® 10 milligram, MERCK SHARP & A ; DHOME ) .Compare the pharmacokinetic parametric quantities of both trial and mention preparation.Although several pharmacokinetic surveies of montelukast have been published, merely few surveies are done on bioequivalence ( Sripalakit.
, 2010, Knorr et al.,2010 ) . The present survey will be done to find the pharmacokinetic parametric quantities of two trade names of montelukast tablets in fasting, healthy human voluntaries belonging to Pakistan for the first clip.
In this manner we will be able to find concentration of montelukast and look into effects of geonetic factors on the pharmacokinetics.These parametric quantities will be statistically compared to measure the bioequivalence between the two trade names.Another the concern of this survey is cost-effectiveness. As Singulair, is selling at high monetary value in Pakistan, so by this bioequivalence survey it can be ensured that locally manufactured drugs produce the same effects at low monetary value rate as Singuilar do.