THE CLINICAL PHARMACOKINETIC STUDIES ON ORAL DANAZOL CAPSULES IN CHINESE VOLUNTEERS

Two danazol capsule formulations were given orally to nine healthy female volunteers in a random crossover design. One formulation(A) was imported from USA, and another(B) was a developing formulation product made in China. The two experiments on each volunteer were separated by four weeks at least. Serum danazol concentrations were determined by RPHPLC method. The C×t data were Jitted to One Compartment Open Model with lagtime of absorption by PCNONLIN program, and the population pharmacokinetic parameters for formulation A were calculated by NONMEM program. The pharmacokinetic parameters(SD) for formulation A and B are:V_d/F(KL)=0.740(0.338) and 1.335(0.439); k. (h~(-1))=1.900(2.328) and 1.948(3.611); t_(lag)(h)=0.604(0.515) and 0.962(0.322), k_(el)(h~(-1))=0.297(0.145) and 0.343(0.057), respectively. The population pharmacokinetic parameters for formulation A in Chinese women are: k_a=1.06h(-1), k_(el)=0.324h~(-1), V_d/F=0.960KL.The corresponding ETA value are 1.48h~(-1), 0.367h~(-1) and 0.697KL, respectively. The epsilon value is 0.00103. For formulation A and B the average AUC(ng·h/ml) amount to 1185 and 503.2, respectively, while C_(max)(ng/ml)=169.0 and 74.7, t_(max)(h)=2.5 and 3.5. The relative bioavailability for the Chinese developing product is thus estimated about 0.425.The clinical implications of the above results are discussed.