RESUMEN
OBJECTIVE： To investigate the influential factors of tacrolimus （TAC） blood concentration in patients with nephrotic syndrome （NS） of different nationalities. METHODS： In retrospective study， clinical information of 104 patients who diagnosed as NS and met inclusion/exclusion criteria were collected from the First Affiliated Hospital of Xinjiang Medical University during Dec. 2017 and Nov. 2018， including gender， age， ethnicity， height， body weight， laboratory test items， combined drug use and TAC dosage. Influential factors for TAC blood concentration were analyzed by SPSS 22.0 software， and effects of combined use of Wuzhi capsule on steady-state blood trough concentration （[ss][c min]） and dose of TAC were also analyzed. RESULTS： Among 104 patients， totally TAC blood concentration of 394 case times were monitored； using TAC standardized blood concentration as endpoint， Han nationality group was significantly lower than Uygur and Kazak nationality group （P＝0.003）； patients receiving combined use of Wuzhi capsule were significantly higher than those without combined use of Wuzhi capsule （P＝0.056）； the patients with combined use of calcium antagonists was significantly higher than the patients without calcium antagonists （P＝0.01）； the patients with combined use of proton pump inhibitors were significantly lower than those without combined proton pump inhibitors （P＝0.01）； patients with normal hematocrit were significantly lower than those with abnormal hematocrit （P＝0.001）； patients with normal urea nitrogen were significantly lower than those with abnormal urea nitrogen （P＜0.001）. The dose of TAC in patients receiving combined Wuzhi capsule were significantly lower than those without combined use of Wuzhi capsule （P＝0.001）， there was no significant difference in [ss][c min] of TAC between them （P＝0.29）. CONCLUSIONS： For NS patients， the effects of ethnicity， calcium antagonists， proton pump inhibitors， hematocrit， urea nitrogen and Wuzhi capsules on TAC blood concentration should be considered when TAC is used.
RESUMEN
OBJECTIVE： To establish a method for the determination of harmine derivative DH-330 in rat plasma and to use it for pharmacokinetic behavior evaluation of DH-330 in rats after intragastric administration. METHODS： Using tinidazole as internal standard， after pre-treatment of acetonitrile precipitated protein， UPLC-MS method was adopted to determine the plasma concentration of DH-330. UPLC analysis was performed on Waters ACQUITY BEH C18 column （50 mm×2.1 mm，1.7 μm） with mobile phase consisted of acetonitrile-methanol-0.5％ formic acid aqueous solution（15 ∶ 55 ∶ 30， V/V/V） at flow rate of 0.4 mL/min， while the column temperature was 30 ℃， and sample size was 5 μL. MS analysis was conducted by electrospray ionization source， positive ion scanning， ion source temperature at 124 ℃， DH-330 detection of mass to charge ratio （m/z） of 335.8→334.8， and internal standard m/z of 247.0→81.0. Six Wistar rats were given DH-330 suspension（50 mg/kg） intragastrically. Blood samples were collected from fundus venous plexus capillary before administration （0 h） and 0.25，0.5，1，2，4，6，8，12，24 h after administration. Plasma concentration of DH-330 was determined and plasma concentration-time curves were drawn. Pharmacokinetic parameters were calculated by using Kinetica 5.0 software. RESULTS： The linear ranges of DH-330 were 25.05-2 004 ng/mL（r＝0.999 8），and the limits of quantitation was 25.05 ng/mL. RSDs of intra-day and inter-day were all less than 10％. The accuracy RE was －9.76％ to 4.55％. The extraction recovery was higher than 85％（RSD＜5％）. Stability RE was －2.53％ to 2.29％. They were not affected by matrix effect or residual effect of injection. The pharmacokinetic parameters of DH-330 in rats after intragastric administration included that cmax was （1 162.43±241.72）ng/mL，AUC0-∞ was （3 242.93±652.31）ng·h/mL，t1/2 was （1.93±0.61）h， MRT was （3.23±0.30）h，CL was （16.80±5.30）L/h·kg， Vss was （54.78±19.64）L/kg. CONCLUSIONS： The established method is simple， specific， sensitive， precise and recovery， which can be used for the plasma concentration determination of DH-330 in rats. DH-330 has short half-life， rapid absorption and large apparent distribution volume after intragastric administration in rats， which indicates that it has high lipophilicity and may be mainly distributed in tissues.