Pengaruh perasan rimpang temu putih Curcuma zedoaria (Berg) Roscoe terhadap ketoksikan akut dan kinerja toksikokinetika teofilin pada tikus

FADHOLAH, Amal, Dr. Imono Argo donatus, SU.,Apt

2001 | Tesis | S2 Farmasi

Penelitian antaraksi obat modern dengan obat alami menggunakan senyawa model teofilin dengan perasan rimpang temu putih, dilakukan untuk mengetahui akibat atau dampak toksikologi antaraksinya. Selain itu penelitian ini ditujukan untuk memperoleh data dan informasi tentang keefektifan perasan rimpang temu putih dalam menggeser kinerja toksikokinetika dan ketoksikan akut teofilin. Perasan kering rimpang temu putih dibuat dengan memotong rimpang segar yang telah dicuci, diblender, diperas sarinya, selanjutnya dikeringkan dengan freeze dryer. Sebagian kandungan rimpang dianalisis dengan KLT. Dampak antaraksi dikerjakan dengan rancangan acak lengkap pola searah. Sebanyak 50 ekor tikus putih jantan galur Wistar umur 2,5 bulan dibagi menjadi 5 kelompok sama banyak. Kelompok kontrol diberikan teofilin 300 mg/kg BB dalam CMC 1 % peroral, kelompok perlakuan berturut-turut diberikan perasan rimpang temu putih dalam CMC 1 % dengan kadar 15,75 (P-1); 31,5 (P-2); 63 (P-3) dan 126 (P4) mg/kg BB, 12 jam sebelum pemberian teofilin. Setelah seluruh hewan uji mendapatkan teofilin, gejala dan jumlah kematian tikus dicatat. Farmakokinetika teofilin dikerjakan dengan 30 ekor films jantan Wistar dibagi 5 kelompok. Teofilin kadar 25 mg/kg BB diberikan secara oral, sedangkan kadar perasan temu putih seperti pada uji ketoksikan akut. Pada interval waktu tertentu darah diambil dan pembuluh vena lateralis ekor dan ditampung dalam wadah yang berisi heparin. Kadar teofilin plasma ditetapkan dengan HPLC mengikuti metode Orcutt dick yang dimodifikasi. Parameter farmakokinetika teofilin dihitung dengan program STRIPE, didasarkan metode nonkompartemen. Rata-rata angka kematian tikus (%) dan nilai parameter farmakokinetika dianalisis dengan ANOVA, jika didapatkan perbedaan kontrol dengan perlakuan, dilanjutkan uji berpasangan metode Benferroni. Hasil penelitian menunjukkan bahwa temu putih pada kadar P-1 dan (P-2) berdampak terhadap penurunan jumlah kematian tikus (42,86 % dan 28,55 %). Sebaliknya pada dosis P-3 dan P4, temu putih ternyata meningkatkan jumlah kematian tikus (14,32 dan 57,18 %). Namun hanya pada P4 yang memberikan pengaruh yang bermakna. Hasil uji farmakokinetika teofilin akibat praperlakuan temu putih dosis P-1 dan P-2 adalah peningkatan C1T (31,54 % dan 38,89 %) (p < 0,05) serta penurunan AUC (22,37 % dan 27,22 %) dan t1/2 eliminasi (25,97 % dan 15,72 %) (p > 0,05). Sebaliknya pada P-3 dan P4, temu putih menghambat CIT teofilin (6,49 % dan 28,40 %) (p < 0,05) sehingga AUC meningkat (8,84 dan 41,02 %) dan t1/2 eliminasi diperpanjang (31,21 % dan 85,87 %). Adapun Ka, Cmaks, tmaks dan Vd relatif tidak berubah akibat praperlakuan temu putih. Praperlakuan temu putih pada teofilin ternyata berdampak berlawanan antara dosis kecil dan besar, dengan demikian tidak ada hubungan yang tinier antara kenaikan dosis temu putih dengan angka kematian tikus maupun pergeseran nilai CIT, AUC, serta t1/2 eliminasi dan teofilin.

The interaction between theophylline and sequeezing of white turmeric rhizome was studied to understand ultimate result of interaction or toxicological effect. Further investigation have been done to study the efectivity sequeezing of white turmeric on interfearing toxicokinetics and acute toxicity of theophylline. The fresh rhizome were washed, blended, sequeezed and dried with freeze dried to get dry sequeez. A part of chemicals compound was analyzed by TLC. In order to study acute toxicity, fifty male Wistar rats were divided randomly into five groups of ten animals. To the rats of control group, oral theophylline (300 mg/kg bw in CMC 1 %) were administered orally. The animals in group treatment were given by sequeeze of white turmeric 15,75 (P-1); 31,5 (P-2); 63 (P-3) and 126 mg/kg bw (P.4) in CMC 1 %, twelve hour before theophylline administered. Sign and mortality of rats were observed for twenty four hour. Pharmacokinetics study were done by 30 male Wistar rats which was devided randomly into five groups of six animals. Control group was given orally theophylline in CMC 1 % (25 mg/kg bw), while the animals in group treatment with sequeezed like toxicity study. Blood samples were subsequently withdrawn from the tail veint at various time intervals and collected into heparinized tubes. The concentrations of theophyline blood were determined by Orcutt method with modification and analyzed by HPLC. The concentration-time data were the used to calculate the pharmacokinetic parameters values of theophylline using a STRIPE software with noncompartmen method. Mortality rate (%) and phannacokinetic parameter values were analyzed by ANOVA and continued with Benferroni method if any different were found. The result have shown that the mortality rate was decreased (42,86 % and 28,55 %) (p>0,05) by P-1 and P-2 of sequeezed. On the other hand, the large dose at P-3 and P-4, were increased mortality rats for 14,32 % (p>0,05) and 57,18 % (p<0,05). White tumeric at P-1 and P-2 were able to enhanced significantly Or (31,54 % and 38,89 %) which were followed by decreased of AUC (22,37 % and 27,22 %) and t'/2 elimination (25,97 % and 15,72 %). At P-3 and P4, white turmeric also inhibited the clearance of theophylline (6,49 % and 28,40 %) which resulted sign of AUC (8,84 % and 41,02 %) and t1/2 elimination (31,21 % and 85,87 %). Ka, C.d., tmaka and Vd however only slighty altered by the all doses of white turmeric. White turmeric treatment with any doses showed no linear correlation between doses and mortality rate, this was suggested that there was alteration in Cl-r, AUC and t1/2 elimination of theophylline, because any doses white turmeric treatment in any doses showed no (good) correlation between small and the large dose.

Kata Kunci : teofilin, temu putih, ketoksikan akut dan farmakokinetika, theophylline, white turmeric, acute toxicity, pharmakokinetic