ABSTRACT
OBJECTIVE To investigate the effects of omeprazole on pharmacokinetic parameters of imatinib in rats. METHODS According to body weight， the rats were divided into imatinib+low-dose， medium-dose， and high-dose omeprazole groups， imatinib group， with 6 rats in each group. They were given omeprazole suspension at the doses of 1.8， 3.6 and 7.2 g/kg， or 0.5% sodium carboxymethyl cellulose solution intragastrically respectively； one hour later， imatinib suspension was administered by oral gavage at a the dose of 10 mg/kg. Blood sample （100 μL） was taken from the orbit before and 0.5， 1， 2， 2.5， 3， 4， 5， 6， 8， 12， 24 and 36 hours after intragastric administration of imatinib. Using imatinib-d3 as internal standard， the plasma concentrations of imatinib and its metabolite N-desmethyl imatinib in rat were determined by high performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were calculated by DAS 2.0 software and compared. RESULTS Compared with imatinib group， AUC0－∞ and AUMC0－∞ of imatinib in rat plasma of imatinib+medium-dose omeprazole group， cmax， t1/2， AUC0－∞ and AUMC0－∞ of imatinib in rat plasma of imatinib+high-dose omeprazole group were all increased or prolonged significantly （P＜0.05）. Compared with imatinib group， AUC0－∞ and AUMC0－∞ of N-desmethyl imatinib in rat plasma of imatinib+medium-dose omeprazole group， and cmax and AUC0→∞ of N-desmethyl imatinib in rat plasma of imatinib+high-dose omeprazole group were decreased significantly （P＜0.05）. CONCLUSIONS Omeprazole may increase the plasma concentration of imatinib in rats and reduce the plasma concentration of N-desmethyl imatinib in rats， which may be associated with inhibiting the metabolism of imatinib.
ABSTRACT
OBJECTIVE：To establish a method for the determination of pyrrotinib concentration in plasma ，and apply it in clinic. METHODS ：After precipitated with methanol ，the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol （containing 0.1％ formic acid ）and water （containing 0.1％ formic acid ）（gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 5 µL. The ion source was electrospray ionization source ，and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3（pyrrotinib）and m/z 494.5→ 393.4（internal standard ），respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS ：The linear range of pyrrotinib were 5-300 ng/mL（r＝0.999 3）. The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30％，and relative errors （REs）ranged －6.70％-5.04％. REs of stability tests were in the range of －1.92％-5.42％. The extraction method ，matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL，with an average plasma concentration of 53.8 ng/mL；there was about 2.54 fold individual difference. CONCLUSIONS ：Established LC-MS/MS method is simple ，sensitive and accurate ，and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.
ABSTRACT
OBJECTIVE:To evaluate the clinical efficacy of Shuanghuanglian injection in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD),and to observe its effects on the plasma levels of C-reactive protein (CRP),procalcitonin(PCT)and interleukin-6(IL-6). METHODS:A total of 100 AECOPD patients were randomly divided into observation group and control group,with 50 cases in each group. Control group received routine treatment,such as controlled oxygen therapy,intravenous dripping of moxifloxacin,bronchodilator for relieving asthma,mucolytic for eliminating phlegm,nu-tritional support. Observation group was additionally given Shuanghuanglian injection 1 ml/(kg·d)added into 5% Glucose injec-tion 250 ml intravenously,qd,on the basis of control group. Treatment course of 2 groups lasted for 10 d. Clinical efficacies of 2 groups were compared as well as the changes of serum levels of CRP,PCT and IL-6 before and after treatment and the occur-rence of ADR. RESULTS:After treatment,total effective rate of observation group was 96.0%,which was significantly higher than 82.0% of control group,with statistical significance(P0.05). After treatment,serum levels of CRP,PCT and IL-6 were de-creased significantly in 2 groups,and those of observation group were significantly lower than those of control group,with statis-tical significance (P0.05). CON-CLUSIONS:Shuanghuanglian injection can effectively improve serum inflammatory factors of AECOPD patients,and shows good clinical efficacy and safety.