Clinical Pharmacokinetic Study Of Isoniazid, Rifampicin And Pyrazinamide

Objective To evaluate the relative bioavailability of domestic Yifuxiarran capsules in healthy volunteers and study the pharmacokinetic of isoniazid, rifampicin, pyrazinamide in patients with peritoneal tuberculosis.Method A study on the relative bioavailability of domestic Yifuxian'an capsules was performed in 18 healthy volunteers. According to the double periodic,cross-over randomized and self-control design,each volunteer was given in single dose of Yifuxianan capsules and imported Rifater tablets contained 600mg RFP,400mg INH and 1250mg PZA alternatively. 13 patients with peritoneal tuberculosis were given 600mg RFP,400mg INH and 1250mg PZA, respectively. The drug concentrations of isoniazid,rifampicin,pyrazinamide in serum were determined by HPLC. The main pharmacokinetics of isoniazid,rifampicin,pyrazinamide were caculated by 3P87 and tested by NDST.Results In Yifuxian'an capsules and Rifater tablets,the Tmax(h), Cmax(ug/ml), AUCo-t (ug/ml.h) of rifampicin were 2.03 ± 0.63, 11.93 ± 2.68, 84.63 ± 18.01 (tested group)and 2.33 ± 0.73, 12.06 ± 2.20, 88.22± 19.67 (control group); the Tmax (h), Cmax(ug/ml), AUCo-t(ug/ml.h) of isoniazid were 1.32 ± 0.64 ,8.78 ± 3.63, 28.77 ± 20.74(tested group) and 1.07 ± 0.51, 10.03 ±4.64, 30.97 ± 22.81 (control group); the Tmax (h) , Cmax (ug/ml), AUCo-t (ug/ml.h) of pyrazinamide were 2.11 ± 1.47,36.28 ± 9.17, 544.87±100.17(tested group)andl.67 ± 0.57,37.07 ± 9.78, 551.04 ±98.98 (control group). The logCmax and logAUCo-t of isoniazid,rifampicin,pyrazinamide in Yifuxian'an capsules were same-effective to those of Rifater tablets by double-single t-test.Compare with imported Rifater, the relative bioavailabilities of rifampicin, isoniazid, pyrazinamide in domestic Yifuxian'an capsules were 97.08% ± 15.12%,96.79% ±26.98%, 100.03%± 16.02% respectively.In patients with peritoneal tuberculosis,the Tmax(h), Cmax(ug/ml), AUCo-t (ug/ml.h) of three drugs were as follow: rifampicin were 2.58 ± 0.63, 11.23 ± 2.28, 91.03 ± 18.01; isoniazid were 1.36± 0.64, 9.05 ± 3.83, 29.94±21.24; pyrazinamide were 2.00 ±0.61, 36.48 ±9.17, 548.87 ±99.67 respectively. By t test, there are no significant differences between the pharmacokinetics of isoniazid, rifampicin, pyrazinamide on healthy volunteers and those of patients with peritoneal tuberculosis (P>0.05).Conclude (1) There are not any significant differences between the main pharmacokinetics of rifampicin,isoniazid, pyrazinamide in Yifuxian'an capsule and those of Rifater by t test(P>0.05). LogCmax, logAUCo-t of isoniazid, rifampicin, pyrazinamide in the domestic Yifuxianan capsule and imported Rifater tablets are bioequivalent by double-single t-test. (2) In healthy volunteers and patients with peritoneal tuberculosis, pharmacokinetics of isoniazid, rifampicin, pyrazinamide abide by single-compartment model. There are not any significant differences between the main pharmacokinetics of rifampicin,isoniazid, pyrazinamide in healthy volunteers and those of patients with peritoneal tuberculosis by t test (P>0.05) .So,we can think that patients with peritoneal tuberculosis have as same metabolism and elimination as healthy volunteers, when patient's functions of liver and kidney are normal.