According to foreign literature, the serum concentration of total pioglitazone (pioglitazone and its active metabolites) is still high after 24 hours of oral administration of 1 time/day. Within 7 days, pioglitazone and total pioglitazone reached the steady-state serum concentration. In the steady state, the serum concentrations of two pharmacologically active metabolites of pioglitazone, metabolites ⅲ (M-ⅲ) and ⅳ (M-ⅳ), reached or exceeded the level of pioglitazone. In healthy volunteers and patients with type 2 diabetes mellitus, pioglitazone accounts for 30% ~ 50% of the total peak concentration of pioglitazone and 20% ~ 25% of the area under the plasma concentration-time curve (AUC). When 1.5mg/ day and 30mg/ day were given respectively, the peak serum concentration (Cmax), AUC and serum concentration (Cmin) of pioglitazone and total pioglitazone increased proportionally. However, when the dosage is 60mg/ day, the increase of pioglitazone and total pioglitazone is slightly lower than this ratio. Absorption: After oral administration, pioglitazone can be detected in serum 30 minutes after fasting, and the peak concentration can be reached 2 hours later. Food will delay the peak time to 3-4 hours, but it will not change the absorption rate. Distribution: The average apparent distribution volume (Vd/F) of pioglitazone after a single dose was 0.63+0.4 1 (mean+standard deviation) L/kg body weight. In human serum, the binding rate of pioglitazone protein is very high (]99%), mainly with serum albumin, but also with other serum proteins, but the affinity is low. The binding rate of metabolites M-Ⅲ and M-Ⅳ with serum albumin is also very high (]98%). Metabolism: Pioglitazone is metabolized by hydroxylation and oxidation, and its metabolites are also partially converted into glucuronic acid or sulfuric acid conjugate. In the animal model of type 2 diabetes, the metabolites M-Ⅱ, M-Ⅳ (hydroxylated derivatives of pioglitazone) and M-Ⅲ (ketone metabolites of pioglitazone) have pharmacological activities. After repeated administration, except pioglitazone, the main drug forms in human serum are M-ⅲ and M-ⅳ. In the steady state, pioglitazone accounts for 30% ~ 50% of the total peak blood concentration and 20% ~ 25% of the total AUC in healthy volunteers and patients with type 2 diabetes. When incubated with human P450 or human liver microsomes, pioglitazone mainly forms M-Ⅳ and a small amount of M-Ⅱ. In the liver metabolism of pioglitazone, the main isoenzymes of cytochrome P450 are CYP2C8 and CYP3A4, and many other isoenzymes including CYP 1A 1 mainly distributed outside the liver also participate in the metabolism. Ketoconazole can inhibit the liver metabolism of pioglitazone with the same molar concentration up to 85% in vitro. Pioglitazone did not inhibit P450 activity when incubated with human P450 liver microsomes. No human studies have been conducted to determine whether pioglitazone can induce CYP3A4 production. Excretion and clearance: After fasting administration, about 15% to 30% of pioglitazone appears in urine. The drugs excreted are mainly metabolites and their conjugates, while the renal clearance rate of pioglitazone can be ignored. According to research, most oral drugs are excreted into bile in the form of prototypes or metabolites and removed from feces. The average serum half-lives of pioglitazone and total pioglitazone were 3 ~ 7 hours and 65438 06 ~ 24 hours, respectively. The apparent clearance rate (CL/F) of pioglitazone is 5 ~ 7 liters/hour. Renal Insufficiency in Special Population: In patients with moderate renal insufficiency (creatinine clearance rate of 30-60ml/min) to severe renal insufficiency (creatinine clearance rate of [30ml/min]), the serum clearance half-lives of pioglitazone, M-Ⅲ and M-Ⅳ are the same as those of normal people. Patients with renal insufficiency do not need to adjust medication. Hepatic insufficiency: Compared with the normal control group, the average peak concentration of pioglitazone and total pioglitazone in patients with hepatic insufficiency (Child-pugh grade B or C) decreased by about 45%, while the average AUC value remained unchanged. Pioglitazone hydrochloride should not be used for treatment if the patient has clinical evidence of active liver disease or the level of serum transaminase (ALT) exceeds 2.5 times the normal upper limit (see main items, effects on liver). Elderly people: Compared with young people, the peak plasma concentrations of pioglitazone and total pioglitazone in healthy elderly people have no obvious change, with a slightly higher AUC value and a slightly longer final half-life. These changes have no important clinical significance. Children: Pharmacokinetic data of children are unknown. Gender: Among women, the average Cmax and AUC values have increased by 20% to 60%. Pioglitazone hydrochloride can improve blood sugar control in men and women, whether used alone or in combination with sulfonylureas, metformin or insulin. In controlled clinical trials, the baseline concentration of glycosylated hemoglobin, namely hemoglobin A 1C(HbA 1C), decreased more in women than in men (the average difference of HbA 1C was 0.5%). In order to achieve good blood sugar control, the treatment should be individualized, but there is no need to adjust the dose just because of gender differences. Race: Pharmacokinetic data of different races have not been obtained.