Clinical Research Of Cyclophosphamide Drug Metabolism In Children With Lupus Nephritis

Objective: 30 cases of children with LN were treated with cyclophosphamide,blood samples were collected at different time points after the first treatment.The clinical indicators and evaluation of therapeutic effects,adverse drug reactions,analysis of factors affecting the pharmacokinetics and therapeutic effects,adverse reactions,thus early intervention to improve treatment and reduce adverse reactions.Methods: 30 patients received treatment of children hospitalized LN patients in this study were collected from January 2014 to December 2016 in Tianjin Children's Hospital Department of immunology,all patients were first diagnosed,the patients were recorded before treatment,clinical information,collection index.All patients were treated with hormone and cyclophosphamide,and the blood samples were collected after the first intravenous infusion of cyclophosphamide.The blood sampling points were 0.5h,1H,4h,12 h,24h,36 h after infusion.The chromatographic column was Hypersil ODS-2 C18 column,the mobile phase was acetonitrile water?volume ratio of 30:70?,the flow rate was 1 ml/min,the column temperature was at the temperature of 30 DEG C,the detection wavelength was 195 nm,the sample size was about 20 L.With ifosfamide as internal standard,plasma proteins were precipitated with methanol and centrifuged supernatant sample detection.To establish a high performance liquid chromatography?HPLC?method to monitor the blood concentration of cyclophosphamide at various time points and calculate the pharmacokinetic parameters.All patients were followed up for 24 weeks,and plasma albumin?ALB?,urinary protein excretion,serum creatinine?Scr?,complement,clinical remission and SLEDAI score were evaluated at the end of the study.The patients were followed up for 24 weeks.The application of statistical methods,effective hormone therapy combined with cyclophosphamide,and analyze the relationship between treatment effect,SLEDAI score and pharmacokinetics,analysis of factors affecting the clinical indicators affect the pharmacokinetics and adverse reaction.So as to predict the effect of treatment and take clinical intervention measures,so as to obtain the best therapeutic effect,shorten the treatment time and reduce the occurrence of adverse reactions.Results: All patients received 16 weeks of follow-up after treatment reached partial remission in patients with a total of 7 cases?23.22%?,22 cases of complete remission?73.33%?,invalid in 1 cases?3.33%?;24 weeks follow-up of partial remission in patients with a total of 6 cases?20%?),24 cases of complete remission?80%?,no relief.Effective treatment.Plasma cyclophosphamide at 0.5 20 mg/L range,linear peak area and internal standard was good?r=0.999 4?,the lowest detection limit was0.05 mg/L;the relative standard deviation?RSD?in the intra day and inter day precision and stability experiments were <8%;the rate of recovery was 100.60% ¹01.05% satisfactory results.Adverse reactions included reduction in white blood cells?10%?,gastrointestinal symptoms?13.33%?and respiratory tract infections?20%?.AUC 143.55±42.43 g L^-1.h,Cmax 20.02±3.55 g.L^-1,T1/2 4.21±0.96 h.Age,weight had no effect on AUC,Cmax,T1/2,ALB had an effect on T1/2?P<0.05?,the higher the plasma albumin,the longer the T1/2.Scr,complement,SLEDAI score had no effect on pharmacokinetics.T1/2,AUC and Cmax had no effect on clinical remission.There was no significant difference in the incidence of adverse events,and there was no significant difference between age,body weight,blood biochemical index,SLEDAI score and adverse reactionConclusion: The effect of hormone combined with low dose cyclophosphamide on children with LN was satisfactory,and no serious adverse reactions were observed.The HPLC method can be used to detect the concentration of cyclophosphamide.The method is simple,rapid and accurate.Plasma albumin has an impact on T1/2 T1/2,the longer the better treatment,the main factors caused the decrease of albumin is the urinary protein before treatment,thus increase the serum albumin level maybe beneficial to improve the therapeutic effect.There was no effect on the occurrence of adverse drug reaction?ADR?by pharmacokinetic and biochemical parameters and disease activity.