Evaluation of Terbinafine Activity on Pneumocystis carinii in the Rat Model

Objective: The purpose of this study was to test the hypothesis thThis study was planned to investigate the antipneumocystis activity of terbinafine in a rat model. Material and Methods: Rats were obtained from the Hakan Cetinsaya Experimental and Clinical Research Institutions, Erciyes University, Kayseri, Turkey. Terbinafine administered orally in doses of 40, 80, 120 and 160 mg/kg/day after nine weeks of immunosuppression with dexamethasone to facilitate the development of acute Pneumocystis carinii penumoniae (PCP). Results: Untreated animals showed P. carinii infection levels with a mean (aplusmn;standard deviation) log number of cysts per gram of lung tissue of 4.6aplusmn;1.6 at the end of the experiment. Terbinafine administered at a dose of 160 mg/kg/day significantly reduced the log number of cysts per gram to 2.2aplusmn;1.5. The therapeutic efficacy of terbinafine administered at 160 mg/kg/day (log 2.2aplusmn;1.5 cysts/lung) was similar to that obtained with trimethoprim-sulfamethoxazole (TMP-SMX), 50/250 mg/kg/day (palt;0.001). A reduction in the number of cysts was also observed in infected animals treated with 80, and 120 mg of terbinafine/kg/day, although the results were not statistically significant (pagt;0.05). Conclusion: In our model, the efficacy of terbinafine in PCP has been found to be dose dependent. Turkish Baslik: Pneumocystis cariniia#39;ye Terbinafinin Etkisinin Rat Modelinde Degerlendirilmesi Anahtar Kelimeler: Pneumocystis carinii; rat modeli; terbinafin Amac: Bu calisma rat modelinde terbinafinin anti-Pneumocystis aktivitesini belirlemek icin planlanmistir. Gerec ve Yontemler: Ratlar Erciyes Universitesi Deneysel ve Klinik Arastirma Merkezina#39;den saglanmistir. Dokuz hafta boyunca akut Pneumocystis carinii pnomonisi (PCP) olusturmak uzere, deksamethazon ile immunsupresyon yapilan ratlara oral olarak 40, 80, 120 ve 160 mg/kg/gun terbinafin verildi. Bulgular: Calismanin sonunda tedavi almayan grupda PCP enfeksiyon duzeyi ortalama (aplusmn;standart sapma) akciger dokusu gramindaki kist sayisi log 4.6aplusmn;1.6 idi. Terbinafin 160mg/kg/gun uygulanan grupta gramdaki kist sayisinda onemli dusus gozlendi log 2.2aplusmn;1.5. Terbinafin 160mg/kg/gun uygulanan tedavi etkinligi, trimetoprim-sulfametoksazol (TMP-SMX), 50/250 mg/kg/gun uygulamasi ile benzer sonuc verdi (palt;0.001). Terbinafin 80 ve 120 mg/kg/gun uygulamalarinda da kist sayisinda dusus gorulmekle birlikte bu degerler istatistiksel olarak anlamli degildi (pagt;0.05). Sonuc: Bizim modelimizde terbinafinin PCP etkinligi doza bagli bulundu.