Proguanil Dapsone

Dapsone, an aromatic sulfone, is administered in combination with a proguanil derivative. Dapsone... 

Different antimalarials selectively kill the parasite s different developmental forms. The mechanism of action is known for some of them pyrimethamine and dapsone inhibit dihydrofolate reductase (p. 273), as does chlorguanide (proguanil) via its active metabolite. The sulfonamide sulfadoxine inhibits synthesis of dihydrofolic acid (p. 272). Chlo-roquine and quinine accumulate within the acidic vacuoles of blood schizonts and inhibit polymerization of heme, the latter substance being toxic for the schizonts. 

Mefloquine, chloroquine, proguanil, and pyrimethamine plus dapsone (Maloprim), alone or in combination are most commonly advised for prophylaxis regimens and doxycycline for special cases (drug resistance or intolerance) primaquine is being re-evaluated. 

Considering the drugs in relation to modes of action, dapsone and the sulphonamides block the biosynthesis of tetrahydrofolate by inhibiting di-hydropteroate synthetase, while the 2,4-diamino-pyrimidines (proguanil and pyrimethamine) block the same pathway but at a later step catalysed by dihydrofolate reductase. 

Drugs used in prophylaxis. These block a stage in the life cycle, e.g. chloroquine, dapsone, doxycycline, mefloquine, proguanil and pyrimethamine, and often in combinations. 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Classification and pharmacokinetics The antifolate group includes pyrimethamine, proguanil, sulfadoxine, and dapsone. All of these drugs are absorbed orally and are excreted in the urine, partly in unchanged form. Proguanil has a shorter half-life (12-16 hours) than other drugs in this subclass (half-life > 100 hours). 

No pharmacokinetic interaction appears to occur between dapsone and proguanil, and they have been successfully used together for malaria prophylaxis. 

Edstein MD, Rieckmann KH. Lack of effect of proguanil on die phannacc dnedcs of dapsone in healdiy volunteers. Chemo ercqjy (1993) 39, 235-41. 

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