Pyrimethamine does not significantly affect pharmacokineticsof dapsone
Clinical evidence,mechanism, importance and management
A study in 7 healthy subjects given single doses of dapsone 100 mg, pyrimethamine 25mg or both drugs together found that peak plasma levels of dapsone fell by 17 % and half-life was unchanged, but apparent volume of distribution was significantly increased from 1.53 to
1.93 L/kg. The pharmacokinetics of pyrimethamine were not affected by dapsone (See reference number 1). In another study HIV-positive patients were given dapsone 200mg weekly (the maximum tolerated dose) either alone or with pyrimethamine 25mg weekly. In contrast to earlier study, there was a decrease in volume of distribution of dapsone when it was given with pyrimethamine, although dapsone levels were not significantly altered (See reference number 2). Furthermore, tolerability of one-weekly dapsone plus pyrimethamine was found to be similar to that of once-weekly dapsone alone (See reference number 2).
Ahmad RA,Rogers HJ. Pharmacokinetics and protein binding interactions of dapsone and pyrimethamine. Br J Clin Pharmacol (1980) 10, 519–24.
Falloon J,Lavelle J, Ogata-Arakaki D, Byrne A, Graziani A, Morgan A, Amantea MA, OwnbyK, Polis M, Davey RT, Kovacs JA, Lane HC, Masur H, MacGregor RR. Pharmacokinetics andsafety of weekly dapsone and dapsone plus pyrimethamine for prevention of pneumocystispneumonia. Antimicrob Agents Chemother (1994) 38, 1580–7.