Pharmacokinetics of tetroxoprim and sulphadiazine in human volunteers

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Abstract
The pharmacokinetics of tetroxoprim (TXP) and sulphadiazine (SDZ) were studied in healthy volunteers. In a single dose study TXP and SDZ were given alone and in combination. No interaction could be detected as a result of combined administration. The data was fitted for both drugs by computer analysis to a one-compartment model. After a dose of 80 mg orally. TXP was observed to have a mean plasma half-life of 5· 1 h. The mean peak concentration was 1·7 mg/1 at 2·5 h. The half-life of renal excretion of unchanged TXP was 6·7 h, with a recovery of 40 to 60%. Urine concentrations ranged 30 to 70 mg/1 in the first 4 h after the dose. The mean plasma half-life of SDZ was 12·6 h, with a mean peak concentration of 16 mg/1 at 3·5 h. Urinary recovery of unchanged SDZ was 65 to 70% of the dose, giving concentrations of 100 to 200 mg/1. Total recovery of unchanged plus metabolised drug was 94 to 102%. After repeated doses of TXP 160 mg 12-hourly, a steady-state was reached in 24 h giving peak concentrations of 4-4 mg/1 and nadir concentrations of 1·2 mg/1. The steady-state for SDZ was reached after 48 h of dosing at 400 mg 12-hourly orally, the concentrations being about twice as great as those following initial doses. The plasma half-lives for SDZ did not alter significantly between the first and 4th days of dosing. A study was conducted to ensure that TXP had no inducing effect on human metabolism. No changes in plasma antipyrene half-life, urinary D-glucaric acid excretion, or TXP plasma half-life were detected during eight days' dosing with TXP 80 mg 12-hourly. The bioavailabilities of TXP and SDZ from tablet and syrup formulations were compared. They appeared to be identical for TXP; neither were there differences with SDZ between the formulations, apart from a slightly lower mean peak plasma concentration with the syrup. Although this reached the level of statistical significance, it was felt that further studies were needed before any conclusion could be drawn.

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