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OBJECTIVE To investigate the effects of CYP3A5 gene polymorphism and Wuzhi capsule （WZ） on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients. METHODS A total of 132 patients who underwent renal transplantation and received tacrolimus + mycophenolic acids + prednisone after operation in our hospital from September 2021 to September 2023 were selected and divided into four groups according to genotypes （CYP3A5*1 or CYP3A5*3/*3） and with or without WZ （“ +WZ” meant drug combination， “ +NO WZ” meant without combination）. The blood trough concentration/daily dose （c0/D） values of the four groups were analyzed on the 14th day， 1 month and 3 months after renal transplantation. The incidence of acute rejection and the incidence of tacrolimus-related adverse reactions within 3 months after transplantation were compared among 4 groups. RESULTS On the 14th day， 1 month and 3 months after surgery （except for the CYP3A5*1+WZ group）， c0/D values of CYP3A5*1 genotype patients were significantly lower than those of CYP3A5*3/*3 genotype patients regardless of whether they were treated with WZ additionally （P＜0.05）. Within 3 months after surgery， although there was no significant difference in the incidence of acute rejection and tacrolimus-related adverse reactions among the four groups （P＞ 0.05）， the incidence of hyperglycemia in patients with CYP3A5*3/*3 was higher （41.67%）. CONCLUSIONS CYP3A5 gene polymorphism is significantly related to tacrolimus c0/D in kidney transplant patients. Under the premise of c0 monitoring of tacrolimus， patients with CYP3A5*1 genotype should be given WZ as soon as possible after surgery to accelerate tacrolimus to reach the therapeutic concentration range， while CYP3A5*3/*3 genotype is not recommended to be given WZ because of the higher risk of hyperglycemia.
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AIM: To explore the clinical efficacy of three different kinds of Chinese patent medicines combined with tacrolimus and hormone in the treatment of nephrotic syndrome (NS). METHODS: A total of 199 patients with NS treated in department of nephrology of our hospital from January 2018 to December 2020 were analyzed retrospectively. All patients were treated with tacrolimus combined with hormone regimen for 12 weeks. According to different treatment schemes, they were divided into 4 groups: 57 cases in the control group, 51 cases in the Bailing capsule group (Bailing group), 55 cases in the Huangkui capsule group (Huangkui group) and 36 cases in the Wuzhi capsule group (Wuzhi group). The general data of patients, the biochemical indexes before and after treatment, and the tacrolimus blood concentration were collected. RESULTS: After 12 weeks of treatment, 24 h UTP and ALB of each group were statistically different (P<0.01). Compared with the control group, Bailing group had statistically significant differences in the reduction of TG and TC (P<0.05), Huangkui group had statistically significant differences in the reduction of 24 h UTP and serum TC (P<0.05), Wuzhi group had statistically significant differences in the reduction of 24 h UTP and AST (P<0.05). The steady-state trough concentration (C
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To determine the relationship between the effect of wuzhi capsules on the blood concentration of tacrolimus as compared to diltiazem and with regard to cytochrome P450 (CYP)3A5 gene polymorphisms, 170 patients who underwent renal transplantation from November 2014 to March 2018 and used tacrolimus combined with diltiazem 30 mg bid were selected in this study retrospectively. Patients were divided into an observation group (105 patients) and a control group (65 patients) according to whether they used wuzhi capsules after the operation. The polymorphisms of CYP3A5*3 were determined and the effect of wuzhi capsules on the blood concentration of tacrolimus, as compared with that of diltiazem was determined in patients with different CYP3A5*3 genotypes. This study complies with relevant ethical norms. The results show that compared with diltiazem, an increase of tacrolimus C0/D was significantly correlated with the patient's CYP3A5*3 genotype in both the self-control and the control group. CYP3A5 expressers in the observation group were able to increase the tacrolimus C0/D by about 76.8% by replacing the wuzhi capsules with diltiazem, but this effect was not observed in CYP3A5 non-expressers. In CYP3A5 expressers wuzhi capsules had a greater ability relative to diltiazem to increase the blood concentration of tacrolimus.
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OBJECTIVE: To study the effects of Wuzhi capsule/schisantherin A (SchA) combined with cyclophosphamide on the pharmacokinetics of cyclophosphamide (CTX) in rats. METHODS: A total of 36 rats were randomly divided into CTX group (via tail vein, iv, CTX solution 300 mg/kg), CTX+WZC group (ig, Wuzhi capsule 300 mg/kg+via tail vein, iv, CTX solution 300 mg/kg), CTX + SchA low-dose, medium-dose, high-dose and excessive high-dose groups (ig, SchA 30, 300, 3 000, 30 000 μg/kg+via tail vein, iv, CTX solution 300 mg/kg) with 6 rats in each group. Blood samples were collected from orbital venous plexus of rats before medication and 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 h after medication.UPLC-MS/MS method was applied for concentration determination of CTX and its metabolites [de-chloroethyl CTX (DC-CTX), 4-ketone CTX (4-keto CTX), carboxyl phosphamide (CPM)] in plasma of rats. The plasma concentration-time curve was obtained. The pharmacokinetic parameters were fitted by using DAS 2. 0 software. RESULTS: The maximum plasma concentration (cmax) of DC-CTX in CTX group, CTX+WZC group, CTX+SchA low-dose, medium-dose, high-dose and excessive high-dose groups were (22 167. 85 ±2 844. 93), (10 920. 53 ± 1 490. 89), (18 951. 29 ± 1 558. 81), (18 622. 08 ± 791. 19), (18 515. 20 ± 2 560. 61), (15 133. 21 ± 1 305. 07) μg/mL, respectively; the area under the curves (AUCo-48 h) were (173 864. 01 ± 65 342. 21), (100 996. 98 ± 33 530. 02), (137 028. 16 ± 45 975. 19), (131 650. 18 ± 53 196. 41), (113 699. 40 ± 34 131. 36), (110 773. 27 ± 30 307. 15) μg·mL/h, respectively. Compared with CTX group, cmax of DC-CTX in CTX group, CTX+SchA low-dose, medium-dose, high-dose and excessive high-dose groups were decreased by 50. 74％, 14. 51％, 16. 10％, 16. 48％, 31. 73％, respectively. AUC0-48 h were decreased by about 42. 23％, 21. 45％, 24. 63％, 33. 37％, 36. 55％, respectively; with statistical significance (P<0. 05). The pharmacokinetic indexes as t1/2, tmax had no significant change. CONCLUSIONS: To some degree, both WZC and SchA can reduce the generation of DC-CTX, which indicates both of them can inhibit CTX toxicity metabolism pathway so as to reduce the generation of toxic metabolite chloroacetaldehyde. The inhibitory effect of SchA on toxicity metabolism pathway is weaker than that of WZC, and does not have a dose-dependent inhibitory effect.
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Objective To compare the effect of Compound Wurenchun Capsule (CWC) and Wuzhi Capsule (WZC), CWC single and long-term administration on the pharmacokinetics of tacrolimus (FK506). Methods Twenty-four rats were randomly divided into FK506, CWC + FK506, WZC + FK506 and CWC7d + FK506 groups, with six rats in each group. Rats in FK506, CWC + FK506, and WZC + FK506 groups were given a single gavage with FK506, CWC + FK506, and WZC + FK506 respectively. Rats in CWC7d + FK506 group was given a multiple gavage regimen of daily CWC gavage for 6 d, CWC and FK506 on day 7. Blood sample from orbit before and after gavage at different time points (CWC7d + FK506 group before and after the last administration) were tested for FK506 blood concentration and the pharmacokinetic parameters were calculated. Results Compared with FK506 group, peak blood concentration (Cmax) and area under the curve (AUC0-t) of FK506 increased significantly (P < 0.05, 0.01), body retention time (MRT0-t) of FK506 prolonged significantly (P < 0.05, 0.01), the apparent volume of distribution (V/F) and the drug elimination rate (CL/F) of FK506 decreased significantly (P < 0.01) in WZC + FK506 and CWC + FK506 groups. Compared with WZC + FK506 group, AUC0-t of FK506 increased significantly (P < 0.01), CL/F of FK506 decreased significantly (P < 0.01) in CWC + FK506 group. Compared with CWC + FK506 group, Cmax of FK506 increased significantly (P < 0.01), time to peak blood concentration (tmax) of FK506 shortened significantly (P < 0.05), AUC0-t of FK506 increased significantly (P < 0.05), CL/F of FK506 decreased significantly (P < 0.05) in CWC7d + FK506 group. Conclusion Both CWC and WZC can increase Cmax and AUC0-t, prolong MRT0-t, reduce V/F and CL/F of FK506. CWC is better than WZC in increasing AUC0-t and inhibiting CL/F of FK506. CWC long-term administration is better than single-dose in improving Cmax, AUC0-t and reducing tmax of FK506.