Tinjauan Farmakogenomik Rifampisin Dalam Pengobatan Tuberkulosis Paru

Ondri Dwi Sampurno

Abstract


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.

Key words: Pharmacogenomic, Rifampicin, Tuberculosis

Abstrak

Farmakogenomik adalah ilmu yang mempelajari pengaruh genetik terhadap variasi antar individu pada respon obat. Pengaruh genetik tiap individu terhadap respon obat ditunjukkan dengan adanya variasi berkisar 20--95% pada peruraian obat dalam tubuh dan efeknya. Efektivitas rifampisin sebagai bakterisida terhadap Mycobacterium tuberculosis (M.tb.) sangat bergantung pada konsentrasi rifampisin dalam plasma. Peningkatan dosis akan diikuti dengan peningkatan konsentrasi rifampisin dalam plasma di atas konsentrasi hambat minimal (MIC) M.tb dapat menginduksi lebih cepat efek bakterisida terhadap M.tb dan diindikasikan dengan outcome klinis (konversi dahak). Pada standar terapi tuberkulosis,  konsentrasi rifampisin dalam plasma antar pasien TB menunjukkan variasi yang lebar. Variasi antar pasien ini erat kaitannya dengan perbedaan genetik dari masing-masing pasien tersebut. Rifampisin merupakan substrat dari protein polipeptida transporter organik anion (OATP1B1) yang diekspresikan pada membran sinusoidal hepatosit.  Gen solute carrier organic anion 1B1 (SLCO1B1) merupakan gen penyandi OATP1B1 dan diketahui terdapat  variasi urutan gen. SLCO1B1 rs4149032 dan c.463 C>A  dijumpai pada sebagian besar pasien tuberkulosis paru dan berhubungan dengan penurunan kadar rifampisin dalam plasma. Pada subyek Indonesia menunjukkan adanya polimorfisme gen SLCO1B1 SNP c.463C>A dengan frekuensi C 30% dan A 70%. Variasi genetik antar individu ini diduga dapat menyebabkan variasi respon rifampisin antar individu pasien tuberkulosis paru yang berdampak adanya variasi outcome klinis, dalam hal ini konversi dahak.

Kata kunci: Farmakogenomik, Rifampisin, Tuberkulosis


Keywords


Farmakogenomik, Rifampisin, Tuberkulosis

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Jurnal Biotek Medisiana Indonesia (The Indonesian Journal of Biotechnology Medicine, ISSN: 2301-5810. EISSN: 2354-8800) is a journal published by Health Research Center and Development of Biomedical and Basic Health of Technology, National Institute of Health Reseacrh and Development, Ministry of Health of the Republic of Indonesia. Jl. Percetakan Negara No.23 Jakarta Pusat 10560 Indonesia

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