Comparative Bioavailability Study Clinical Trial
Official title:
Influence of Ethnicity and ABCB1 Gene Polymorphism on the Pharmacokinetics of Azithromycin in Healthy Bangladeshi Volunteers: A Preliminary Study.
It is well recognized that different patients respond in different ways to the same medication. These differences are often greater among members of a population than they are within the same person at different times (or between monozygotic twins). The existence of large population differences with small interpatient variability is consistent with inheritance as a determinant of drug response; it is estimated that genetics can account for 20 to 95 percent of variability in drug disposition and effects. Azithromycin is frequently used worldwide irrespective of gender or ethnic populations therefore, to investigate the impact of gender and ABCB1 gene polymorphism holds clinical significance. As a correlation between azithromycin high plasma level and cardiac arrhythmia also exists . If we can prove the variation of pharmacokinetics of azithromycin due to ethnic differences and ABCB1 polymorphism dose adjustment can be done. No relevant study regarding this has been done before in Bangladesh. Therefore, this preliminary study would be of great benefit to formulate the individualized doses regiment design which may improve the efficacy of drug while reducing adverse reaction. At the same time, Genotyping may prove an essential tool for individualized treatment by optimizing the drug dosage for an individual's genetic variability. Further study regarding pharmacogenetics of various drugs may be possible in our country in the future .The present study design to investigate the influence of ethnic difference and gene polymorphism on the pharmacokinetics of azithromycin in Bangladeshi Bangalee and Bangladeshi minor ethnic volunteers.
Individual variation in drug response is a major problem in clinical practices and drug development which ranges from therapeutic failure to adverse drug reaction as drug reaction in multidrug therapy. Pharmacogenetic is relevant in this aspect and mainly concern with the study of genetic variation, which influence individuals' responses to drug. Again, polymorphism (variation) in the genes which are involved in encoding drug metabolizing enzymes, transporters of drug and ion channels can play role in the adverse drug reaction in an individual or can interfere with the therapeutic efficacy. For this reason, now-a-days concept of drug treatment is changed from 'right drug for the right person' to 'right dose for the right person at right time'. The human multidrug resistance gene ATP-binding cassette (ABCB1) codes for P-glycoprotein(P-gp), an important membrane-bound efflux transporter known to confer anticancer drug resistance as well as affect the pharmacokinetics of many drugs and xenobiotics. A number of single nucleotide polymorphisms (SNPs) have been identified throughout the ABCB1 gene that may have effect on P-gp expression levels and functions. Some studies shown an association between ABCB1 gene polymorphism on the pharmacokinetics of azithromycin. Genetic studies to explain this topic is uncommon. On this context, this proposed preliminary study is therefore to investigate the impact of ethnic difference and ABCB1 gene polymorphism on the pharmacokinetics of azithromycin among Bangladeshi people. This study will be a single dose open level comparative pharmacokinetic study, which will be conducted in the department of Pharmacology, BSMMU with the collaboration of Department of Anatomy, BSMMU and Bandarban Sadar Hospital, Bandarban. In this study healthy Bangladeshi volunteers will be divided into two arms-Bangladeshi Bengalese and Bangladeshi minor ethnics residing Chittagong Hill Tracts area, a total of 30 healthy volunteers of aged 20-25 will be provided 500mg oral azithromycin tablet and blood samples will be collected before drug administration (oh) and continuing at time points ,0.5 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 48.0, 72.0 h post dosing.2ml peripheral blood will be collected from each subject to determine the ABC1B gene polymorphism. This proposed study we would attempt to establish a High-Performance liquid Chromatography (HPLC) method to determine the azithromycin in plasma, in order to evaluate the bioavailability of azithromycin. Specific Genotypic polymorphism ABCB1 gene would be determine by Polymerase Chain Reaction-Restriction fragmentation Length Polymorphism Analysis (RFLP-PCR). After estimation of azithromycin and genotyping ABCB1 gene polymorphism, statistical analysis will be done to compare those values. ;