Tinjauan Farmakogenomik Rifampisin Dalam Pengobatan Tuberkulosis Paru

Ondri Dwi Sampurno
Journal article Indonesian Journal of Biotechnology Medicine • 2015 Indonesia

Abstract

Pharmacogenomics is the study of genetic influences of individual variations in drug response. The influence of genetic in drug response has been showed about 20%–95% of variations in drug pharmacokinetics and effects. Activity of rifampicin as bactericidal against Mycobacterium tuberculosis (M.tb.) have been demonstrated plasma concentration-dependent. ‘Concentration-dependent ' means that increasing doses followed by increasing rifampicin plasma concentration above the M.tb's minimum inhibition concentration (MIC) induces more rapid bactericidal effect against the M.tb. indicated by sputum conversion. On standard tuberculosis therapy, among patients have been showed wide intersubject variation of rifampicin plasma concentration. The variation was related to genetic difference among patients. Rifampicin is a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) which is expressed on the sinusoidal membrane of human hepatocytes. OATP1B1 is coded by for the solute carrier organic anion 1B1 (SLCO1B1) gene. A large number of sequence variants have been found in the SLCO1B1 gene. SLCO1B1 rs4149032 and c.463 C>A was present in most patients pulmonary tuberculosis and was associated with substantially reducing rifampicin plasma concentration.The allele frequency of the SLCO1B1 c.463 C>A polymorphism in Indonesian subject was showed C 30% A 70%. Individual genetic variation may cause variation in individual rifampicin response among individual pulmonary tuberculosis patient. It will impact variation in clinical outcome, in this case is sputum conversion.

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Journal

Indonesian Journal of Biotechnology Medicine

Jurnal Biotek Medisiana Indonesia (the Indonesian Journal of Biotechnology Medicine) publishes or... see more