Aim: To study the pharmacokinetics of leflunomide in Chinese healthy volunteers.
Methods: A single (20, 40, and 60 mg) and 30-d -repeated (20 mg/d) oral doses of leflunomide were performed on 18 (12 males and 6 females) and 6 (4 males and 2 females) Chinese healthy volunteers respectively. A771726, the active metabolite of leflunomide, in serum was determined by high performance liquid chromatography (HPLC). Data were analyzed by a 3p97 program on a Legend computer.
Results: Serum concentration curves of A 771726 in single and repeated oral administration of leflunomide conformed to one compartment model of the first order absorption. Leflunomide was absorbed rapidly with T1/2,ka of between 1.15 h and 2.23 h in single oral administration. The major pharmacokinetic parameters of A771726 in 20, 40, and 60 mg groups were T1/2,ke(h): 211 +/- 18, 170 +/- 24, 252 +/- 26; Tmax(h): 13 +/- 12, 13 +/- 4, 9 +/- 5; Cmax (mg/L): 2.0 +/- 0.5, 5.2 +/- 0.6, 6.7 +/- 1.5; AUC (mg . h . L-1): 647 +/- 137, 1344 +/- 191, 2555 +/- 907, respectively. In repeated oral administration, steady stat e concentration was achieved within 30 d. The mean trough concentration was between 32.0 mg/L and 39.7 mg/L. The Cmax, Tmax, AU C0- 24 were (41.5 +/- 2.4) mg/L, (307 +/- 75) h, and (22099 +/- 1234) mg . h . L-1, respectively.
Conclusion: The absorption of leflunomide was rapid, and it s elimination was slow after oral administration. The pharmacokinetic results showed that it exhibited first order kinetic characteristics.