title: Plasma protein binding of sulphadiazine, sulphamethoxazole and trimethoprim determined by ultrafiltration.
abstract: The plasma protein binding of trimethoprim, sulphadiazine and sulphamethoxazole was studied at 37 degrees C by ultrafiltration. Plasma samples contained steady state levels of the drugs from ten volunteers from a cross-over comparative pharmacokinetic study on co-trimazine and co-trimoxazole. The three compounds were determined in plasma and ultrafiltrate by HPLC, the recoveries being close to 100% in each case. Freezing of spiked samples had no influence on the binding. Trimethoprim was 48.5-52.2% bound (mean 50.0%); sulphadiazine was 50.9-60.6% bound (mean 56.2%); and sulphamethoxazole was 74.3-80.8% bound (mean 76.9%). The significantly lower protein binding of sulphadiazine compared to sulphamethoxazole means that equivalent non-protein bound plasma levels of the two sulphonamides are achieved from smaller doses of co-trimazine than co-trimoxazole. Use of co-trimazine may thus minimize the risk of adverse reactions.
authors.affiliation: Astra Läkemedel AB, Research & Development Laboratories, Bioanalytical Chemistry, S-151 85 Södertälje, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Wijkström
authors.forename: D
authors.initials: D
authors.lastname: Westerlund