Clinical research on Cyclophosphamide drug metabolism in children with lupus nephritis

Objective To study the pharmacokinetic status of Cyclophosphamide (CYC) in children with lupus nephritis (LN), as well as the relationship between the pharmacokinetic results and clinical indicators, adverse reactions, curative effect evaluation. Methods Thirty patients hospitalized at Tianjin Children′s Hospital from January 2014 to December 2016 were treated with glucocorticoid (GC) combined with CYC.Blood samples were collected in 6 point-in-time after intravenous CYC, a high performance liquid chromatography (HPLC) method was used to detect the blood drug concentration, and the pharmacokinetic results were calculated. All patients were followed up for 24 weeks, and the levels of serum albumin (ALB), 24 hours urinary protein, serum creatinine (Scr), complement 3 (C3), therapeutic effect and systemic lupus erythematosus disease activity index scores were evaluated at the same time. Results Pharmacokinetic curve showed the second chamber model, the area under the curve (AUC) of time-effect relationship was (143.55±42.43) g/(L·h), peak concentration (Cmax) was (20.02±3.55) g/L, and half-time period (T1/2) was(4.21±0.96) h. Age and gender had no influence on AUC, Cmax and T1/2,and statistically significant correlation was found between serum ALB and T1/2,which was positively correlated (r=0.517, P<0.05). After 16 weeks of treatment, 7 patients were partially responsive, 22 cases had a complete remission, and the invalid case was only one. Followed up for 24 weeks, 6 patients were partially responsive, 24 cases had a complete remission.After 16 weeks of treatment, there were statistical differences in AUC among patients with complete response, partial response or no remission.And after 24 weeks, the patients between complete remission and partial remission had no statistically significant difference in the AUC.After 16 weeks and 24 weeks, T1/2 and Cmax had no statistical diffe-rences among those groups of patients.Adverse reactions included leukopenia (3 cases, 10.00%), gastrointestinal symptoms (4 cases, 13.33%) and respiratory tract infection (6 cases, 20.00%). There was no statistical relationship between pharmacokinetic parameters and the occurrence of adverse reactions.Single factor analysis showed that there was a statistical significance between ALB, urine protein quantity and treatment effect, but multi-factor analysis showed that the relation between factors and therapeutic effect had no statistical significance. Conclusions HPLC method can be used for the detection of cyclophosphamide blood drug concentration. The cyclophosphamide pharmacokinetic status of children and adult is similar.ALB and T1/2 show a linear positive correlation.Single factor analysis shows a correlation between ALB and treatment effect. Therefore, the increasing level of plasma propagated before treatment can improve therapeutic effect possibly.Cyclophosphamide pharmacokinetic status has nothing to do with the occurrence of adverse drug reactions in the study. Key words: Lupus nephritis; Cyclophosphamide; Pharmacokinetics; Treatment; Child