HUBUNGAN KADAR HIDRAZIN (METABOLIT ISONIAZID) DENGAN KADAR SGPT PADA AKHIR FASE INTENSIF PENGOBATAN PASIEN TUBERKULOSIS PARU

AVE OLIVIA RAHMAN, dr. Jarir At Thobari, PhD.; Prof. Dr. Mustofa, Apt., M.Kes.

2013 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar belakang: Pemberian isonizid dalam regimen pengobatan tuberkulosis paru dapat menyebabkan efek samping. Hepatotoksik merupakan salah satu efek samping yang perlu mendapat perhatian. Hidrazin yang merupakan metabolit isoniazid diduga merupakan penyebab hepatotoksik akibat isoniazid. Perbedaan kecepatan asetilasi metabolisme isoniazid menyebabkan perbedaan produksi hidrazin. Studi sebelumnya dengan model hewan coba didapatkan korelasi kadar hidrazin dan kadar SGPT yang merupakan parameter penanda hepatotoksik, sedangkan pada penderita tuberkulosis menunjukkan hasil yang tidak konsisten. Tujuan: Mengetahui korelasi kadar hidrazin dan kadar SGPT 2 jam setelah minum obat akhir fase intensif pada pasien tuberkulosis paru. Metode: Penelitian ini merupakan penelitian observasional dengan rancangan cross-sectional yang diikuti oleh 58 subyek yang merupakan pasien tuberkulosis paru kasus baru. Pengambilan sampel darah dilakukan pada 2 jam setelah minum obat terakhir fase intensif pengobatan tuberkulosis. Status asetilator ditetapkan berdasarkan rasio asetilhidrazin/hidrazin. Penetapan kadar SGPT menggunakan mesin analisis kimia otomatis dan pemeriksaan kadar isoniazid dan metabolitnya, hidrazin dan asetilhidrazin, menggunakan HPLC. Analisis statistik menggunakan uji korelasi. Hasil: Kadar hidrazin secara signifikan lebih tinggi pada asetilator lambat (33,59±5,61 versus 6,36±1,53 ng/mL, nilai p <0,05) dan kadar asetilhidrazin secara signifikan lebih tinggi pada asetilator cepat (0,23±0,03 versus 0,35±0,03μg/mL, nilai p< 0,05). Persentase subyek yang mengalami hepatotoksik sebesar 3,4%. Tidak ada korelasi kadar hidrazin dan kadar SGPT, begitupula tidak ada korelasi kadar hidrazin dan delta SGPT pada 58 subyek penelitian (nilai p <0,05). Pada analisis subgroup berdasarkan status asetilator, ada korelasi yang bermakna antara kadar asetilhidrazin dan delta SGPT (p<0,05, r =0,474) pada kelompok asetilator lambat. Kesimpulan: Tidak ada korelasi kadar hidrazin dan kadar SGPT 2 jam setelah minum obat akhir fase intensif pada 58 subyek penelitian ini.

Background: Isoniazid in the regimen treatment of pulmonary tuberculosis patients causes side effects. Hepatotoxicity is one of isoniazid’s side effects that need medical attention. Hydrazine, a metabolite of isoniazid, was considered as the cause of the development of hepatotoxicity induced by isoniazid. There is a different acetylation speed in the metabolism of isoniazid, causing different hydrazine level among human. In the previous studies with animal models reveals that there was a correlation between hydrazine plasma level and SGPT level as standard hepatotoxicity parameter, but study in human give inconsistent results. Objective: To know the correlation of hydrazine and SGPT levels at 2 hours after drug administration in the end of intensive phase treatment of pulmonary tuberculosis patients. Methods: This was an observational study with cross sectional design followed by 58 subject who were new pulmonary tuberculosis patients. Venous blood sampling was collected at 2 hours after drug administration. Determination of acetylator status using acetylhydrazin/hydrazine ratio. SGPT level was measured with an automatic chemical analyzer. Isoniazid and it’s metabolites, hydrazine and acetylhydrazine was measured by using HPLC. Statistical significance was analyzed using correlation test. Results: Hydrazine level was significantly higher for slow acetylator (33,59±5,61 versus 6,36±1,53 ng/mL, p value <0,05) and acetylhydrazine level was significantly higher for fast acetylator (0,23±0,03 versus 0,35±0,03μg/mL, p value < 0,05). The incidence of hepatotoxicity was 3,4%. There was no correlation between hydrazine level with SGPT levels, neither with delta SGPT in the 58 subjects of this study. In subgroup anaysis by acetylator status, there was significantly correlation between acetylhydrazine level and delta SGPT in slow acetylator group. Conclusions: There was no correlation between hydrazine level and SGPT levels at 2 hours after drug administration in the end of intensive phase in 58 subjects of this study.

Kata Kunci : hepatotoksik, kadar hidrazin, kadar asetilhidrazin, status asetilator