Pustaka Ilmiah Universitas Padjadjaran

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Hubungan antara konsentrasi rifampisin plasma dengan konversi BTA sputum pada penderita TB Paru di Kupang

Tujuan: sputum konversi merupakan salah satu indikator untuk memantau dan mengevaluasi pengobatan tuberkulosis (TB) paru, dipengaruhi oleh berbagai faktor antara lain konsentrasi obat antituberkulosis (OAT). Rifampisin merupakan obat utama pengobatan TB yang memiliki karakteristik concentration and exposure dependent killing activity. Penelitian ini bertujuan untuk mendapatkan gambaran hubungan konsentrasi rifampisin plasma dan konversi sputum pada penderita TB Paru kasus baru di Kupang, Nusa Tenggara Timur. Metode: penelitian ini merupakan penelitian analitik dengan disain cross sectional. Sebanyak 51 penderita TB Paru dewasa, BTA (+) yang berobat di 10 puskesmas di Kupang mengikuti penelitian ini. Konsentrasi rifampisin plasma diukur minimal 2 minggu setelah minum OAT (kondisi steady state). Terhadap 10 subjek pertama, dilakukan pengukuran konsentrasi rifampisin plasma secara serial (pengambilan darah vena dilakukan sebanyak 11 kali dalam 12 jam sejak minum obat) untuk mendapatkan parameter farmakokinetik rifampisin, terutama Area Under the Curve 24 jam (AUC0-24). Kemudian ditentukan konsentrasi pada jam pengambilan tertentu (tp) yang berkorelasi paling erat dengan AUC0-24 dengan teknik analisis menggunakan kurva ROC (Receiver Operating Characteristics). Pada tahap kedua (41 subjek) dilakukan pengambilan sample pada waktu (tp) yang ditemukan pada sampling tahap pertama. Bioanalisis rifampisin dilakukan dengan menggunakan metode tervalidasi dengan alat UPLC (Ultra high Performance Liquid Chromatography) di laboratorium Farmakokinetik, FK Unpad, Bandung. Pemeriksaan mikroskopis BTA sputum dilakukan sebelum pengobatan dan setelah 8 minggu pengobatan dengan metode Ziehl Neelsen yang dilakukan di laboratorium puskesmas setempat. Perbedaan rerata konsentrasi rifampisin plasma pada subjek yang mengalami konversi sputum dan yang tidak mengalami konversi sputum diuji dengan menggunakan Independent t-test, dengan kemaknaan p8 ml/L), sedangkan 62,75% subjek memiliki konsentrasi rendah (subterapetik), bahkan 5,88% memiliki konsentrasi rifampisin yang sangat rendah (< 4 mg/L). Pada akhir fase intensif pengobatan, 83,4% subjek mengalami konversi sputum, 15,6% tidak mengalami konversi. Terdapat perbedaan konsentrasi rifampisin plasma yang bermakna pada kelompok subjek yang mengalami konversi dengan kelompok subjek yang tidak mengalami konversi (7,89 vs. 5,85 mg/L, p= 0,019). Simpulan: terdapat hubungan antara konsentrasi rifampisin plasma dengan konversi sputum pada penderita TB Paru di Kupang.

Objective: Sputum conversion is one of the indicators to monitor and to evaluate tuberculosis (TB) treatment, it is determined by various factors, one of which is the concentration of TB drug, its characteristic is concentration-and exposure-dependent killing. The purpose of this study was to determine the association between rifampicin plasma concentration and sputum conversion in pulmonary TB patient in Kupang, Nusa Tenggara Timur. Methods: An analytical study (Cross sectional design) was conducted involvined, 51 newly diagnosed, smear positive, adult pulmonary TB patients treated at the 10 puskesmas in Kupang. Rifampicin plasma concentration were measured at the steady state ang underwent two step, pharmacokinetics of rifampicin was assessed in 10 subjects by obtaining full pharmacokinetics AUC0-24 and concentration at certain time (tp) that correlated best with AUC0-24 (using ROC analytical approach). At the second step, we collected rifampicin plasma from 41 other subjects taken at (tp). Rifampicin bioanalysis was performed using UPLC at the pharmacokinetic lab, Faculty af Medicine, Unpad. Sputum microscopic examination were performed before starting the treatment and at the end of intensive phase of TB treatment (8 weeks odf treatment), using Ziehl Neelsen methods, Differences in rifampicin plasma concentration were tested with the independent t-test, and p-values of less than 0.05 were judged sisnificant. Results: The mean AUC0-24 was 54.36 mg/L (range 30.59 – 144.25). Subsequent analysis using ROC analytical approach showed that concentration at 3 hours (C3) was correlated best with AUC0-24 so for the next 41 subjects, only C3 was obtained. The mean Rifampicin C3 was 7,57 (2,69) mg/L; the proportion of subjects with terapeutic concentratin of rifampicin was 31.37 %, meanwhile 62.75 % of them were with subterapeutic concentration, and even 5.88 % subject were with very low rifampicin concentration. Sputum conversion was achieved by 83.4 % of subjects. There was a significant different of rifampicin plasma concentration beetwen subject with sputum conversion and those with no sputum conversion (7.89 vs 5.85 mg/L, p = 0.019). Conclusions: It can be concluded that in newly diagnosed, smear positive, adult pulmonary TB patients in Kupang, there is an association between the concentration of rifampicin plasma and the sputum conversion.