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Chlorguanide (proguanil) is combined with atovaquone for malaria prophylaxis. The two compounds act synergistically to inhibit the plasmodial dihydrofolate reductase (DHFR) and interrupt the electron transport chain. Mutations in DHFR account for the development of resistant strains.
| Molecular Weight | 290.19 |
| Formula | C11H16ClN5·HCl |
| CAS Number | 637-32-1 |
| Solubility (25°C) | acetonitrile: water: ~1 mg/mL (60/40) |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[2] G D Shanks, et al. Atovaquone and proguanil hydrochloride for prophylaxis of malaria
[3] P G Kremsner, et al. Atovaquone and proguanil hydrochloride for treatment of malaria
[4] M Beerahee. Clinical pharmacology of atovaquone and proguanil hydrochloride
[5] M Pudney, et al. Atovaquone and proguanil hydrochloride: a review of nonclinical studies
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