Pharmacokinetics of oral co-trimazine and the penetration of its components sulfadiazine and trimethoprim into peripheral human lymph.

Five healthy informed male volunteers received oral doses of 820 mg sulfadiazine (SDZ) plus 180 mg trimethoprim (TMP) (co-trimazine) every 24 h. Concentrations in serum, peripheral lymph from the leg and urine were determined after the first dose, and on the 4th day to reflect approximate steady-state conditions. TMP was assayed microbiologically and unchanged SDZ by high-pressure liquid chromatography. There was a rise in concentrations from the first dose to the 4th day. The rise for SDZ was by a factor of 1.6 in both serum and lymph; the rise for TMP was also 1.6 in serum, but 1.5 in lymph. The peak concentrations at steady state were 27.7 mg/l (SD) +/- 4.3 SDZ, and 1.6 +/- 0.68 mg/l TMP. The serum values at that time were 31.7 +/- 5.8 mg/l SDZ and 2.3 +/- 0.51 mg/l TMP. The simultaneous concentrations of both SDZ and TMP were always somewhat lower in lymph than in serum, also at the end of the observation periods, i.e. 12 h after the first dose and 72 h after the final one. But the serum concentrations of both SDZ and TMP were only slightly higher than in lymph. After the final dose, the ratio between the 12-hour areas under the concentration curves of lymph and serum was 0.68 +/- 0.12 for SDZ and 0.59 +/- 0.14 for TMP. The values after the first dose were similar, 0.63 +/- 0.17 and 0.57 +/- 0.05, respectively. The elimination half-life in serum during steady state was 16.5 h for SDZ, 8.6 h for acetylated SDZ and 9.4 h for TMP. In lymph the corresponding values were 19.2, 19.2 and 8.9 h.