Obiective: P.C seems more closely related to fungi than to protozoans. We have investigated the efficacy of an antiprotozoan and antifungal compound, the terbinafine, together with that of trimethoprim sulphamethoxazole (TMP-SMX), atovaquone (ATQ) and albendazole (ALB) on immunosuppressed rats with established pneumocystosis. Methods: Drugs were administered orally (terbinafine in dosages of 80 mg/Kg/d, TMP 12.5 mg/Kg/d plus SMX 62.5 mg/Kg/d, ATQ 100 mg/Kg/d and ALB 600 mg/Kg/d) to 5 groups each one consisting of 15 rats including controls. Rats were sacrificed and lungs were removed for histological assessment and impression smears (infectivity score). Results: P. carinii pneumonia (PCP) developed in 90% of the controls which exhibited a significantly marked P.C burden and lung’s weight than the other treatment groups. In terbinafine group, P.C infection developed weakly in 2 rats (18%, infectivity score 6±1.2) and histological lung changes were absent or minimal with respect to other drugs. For ALB and ATQ treatment group, the rate of infection were 58.3% and 45.4% with scores 19.4±7.1 and 23±2.1 respectively. In TMP-SMX group, P.C was found in 2 rats (mean score 8±1.1) but rat survival was greater. Conclusions: Terbinafine targets the squalene 2,3 epoxidase with an increased squalene content in fungal cell. This could lead to the disruption of the P.C plasma membrane by a “cidal” effect. Supported by a grant of Italian Ministry of Education (40%) and Sandoz Pharma, Italy.
Evaluation of Anti-Pneumocystis carinii activity of Terbinafine vs atovaquone, albendazole and trimethoprim sulfametoxazole in rat models with Pneumocystosis
CONTINI, Carlo;CULTRERA, Rosario;
1996
Abstract
Obiective: P.C seems more closely related to fungi than to protozoans. We have investigated the efficacy of an antiprotozoan and antifungal compound, the terbinafine, together with that of trimethoprim sulphamethoxazole (TMP-SMX), atovaquone (ATQ) and albendazole (ALB) on immunosuppressed rats with established pneumocystosis. Methods: Drugs were administered orally (terbinafine in dosages of 80 mg/Kg/d, TMP 12.5 mg/Kg/d plus SMX 62.5 mg/Kg/d, ATQ 100 mg/Kg/d and ALB 600 mg/Kg/d) to 5 groups each one consisting of 15 rats including controls. Rats were sacrificed and lungs were removed for histological assessment and impression smears (infectivity score). Results: P. carinii pneumonia (PCP) developed in 90% of the controls which exhibited a significantly marked P.C burden and lung’s weight than the other treatment groups. In terbinafine group, P.C infection developed weakly in 2 rats (18%, infectivity score 6±1.2) and histological lung changes were absent or minimal with respect to other drugs. For ALB and ATQ treatment group, the rate of infection were 58.3% and 45.4% with scores 19.4±7.1 and 23±2.1 respectively. In TMP-SMX group, P.C was found in 2 rats (mean score 8±1.1) but rat survival was greater. Conclusions: Terbinafine targets the squalene 2,3 epoxidase with an increased squalene content in fungal cell. This could lead to the disruption of the P.C plasma membrane by a “cidal” effect. Supported by a grant of Italian Ministry of Education (40%) and Sandoz Pharma, Italy.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
