Employment of terbinafine against Pneumocystis carinii infection in rat models.
The anti-Pneumocystis carinii response of terbinafine together with that of three other compounds, trimethoprim sulphamethoxazole (TMP-SMX), atovaquone (ATQ) and albendazole (ALB), has been investigated in immunosuppressed Sprague-Dawley rats with established pneumocystosis. Drugs were administered orally (terbinafine in dosages of 40 and 80 mg/kg per day, TMP 12.5 mg/kg per day plus SMX 62.5 mg/kg per day, ATQ 100 mg/kg per day and ALB 600 mg/kg per day) to six rat groups except one which served as a control. P. carinii pneumonia (PCP) was identified post-mortem in nine (90%) of the control rats which exhibited a marked P. carinii burden, and mean lung weights were higher with respect to the other treatment groups. During treatment, five rats in the control group died, whereas between 11 and 13 rats in all treatment groups survived. In the terbinafine groups (40 mg and 80 mg/kg per day), a mild P. carinii infection developed in three and two rats (27.2 and 18%), respectively, and almost the same infectivity score was obtained for those treated with 40 mg and 80 mg/kg per day. Histological changes in the lungs in animals receiving terbinafine treatment were minimal. Among the remaining compounds the rate of infection was seven (58.3%) for the ALB treatment group and five (45.4%) for the ATQ group (mean score 19.4 +/- 7.1 and 23 +/- 2.1, respectively). In the TMP-SMX treatment group, there were 13 surviving rats and P. carinii organisms were found in two (15.3%, mean infection score 8 +/- 1.1).
Contini
C
C
Institute of Infectious and Respiratory Diseases, University of Ferrara, Italy.
Colombo
D
D
Cultrera
R
R
Prini
E
E
Sechi
T
T
Angelici
E
E
Canipari
R
R
D000284:Administration, Oral; D015766:Albendazole / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D053626:Atovaquone; D004334:Drug Administration Schedule; D007165:Immunosuppression Therapy; D008168:Lung / Q000473:pathology; D009281:Naphthalenes / Q000627:therapeutic use*; D009285:Naphthoquinones / Q000627:therapeutic use; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077291:Terbinafine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
D000935:Antifungal Agents; D009281:Naphthalenes; D009285:Naphthoquinones; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D015766:Albendazole; D000077291:Terbinafine; D053626:Atovaquone