Pharmacokinetics of co-trimazine after single and multiple doses

Plasma and urinary levels of trimethoprim (TMP), sulfadiazine (SDZ) and N4-acetylsulfadiazine (N4-SDZ) were determined after administration of 1 g co-trimazine (equivalent to 180 mg TMP and 820 mg SDZ) (Kombinax) as a single dose and again once daily for 7 days to 6 normal subjects. Both TMP and SDZ were rapidly absorbed from the gastrointestinal tract with peak plasma levels being achieved within 4 h in all subjects. Elimination half-lives ranged from 8 to 13 h for TMP and from 9 to 15 h for SDZ. Approximately 50% of the administered dose of SDZ was recovered in urine within 24 h of the single dose (32% as unchanged drug and 17% as the N4-acetylmetabolite). For TMP, the urinary recovery during the 24 h following the single dose averaged 39%. Mean plasma levels of TMP, SDZ and N4-SDZ at steady state were moderately higher than those observed after a single dose, but no change in absorption or disposition kinetics of these compounds was seen after repeated dosing.