Objective:To determine the concentration of hydroxychloroquine (HCQ) and its active metabolite deethylhydroxychloroquine (DHCQ) in breast milk of lactating patients with autoimmune disease. To observe the safety of hydroxychloroquine in lactation period, and to explore the factors that may affect HCQ and DHCQ concentration in the milk.Methods:Lactating patients with autoimmune disease who have taken HCQ for at least 6 months were included in our study. A new high performance liquid chromatography (HPLC) method was established to detect HCQ and DHCQ levels in breast milk. Milk samples were collected at different time points: before taking the drug (0 hours), and 2 hours, 4 hours, 6 hours after taking the drug. In addition, the genotype of cytochrome CYP3A4*1G, CYP3A5*3 and CYP2D6*10 which were related to HCQ metabolism were tested by dideoxy chain termination method. Visual acuity, hearing and growth status of the patients' infants were followed up on a regular basis. T-test, one-way ANOVA and Pearson's test were used for data analysis. Results:In 15 patients, the average concentration of HCQ and DHCQ in the milk of patients taking 200 mg/d were (520±261) ng/ml and (177±112) ng/ml, respectively. While the average concentration of HCQ and DHCQ in the milk of patients taking 400 mg/d were (1 036±374) ng/ml and (397±271) ng/ml, respectively. The peak of HCQ level for 11 patients was at 4 hour after taking the drug, while the others' were at 2 hour. The breast-fed infants did not show any abnormal symptoms of hearing, vision and growth. However, cytochrome gene polymorphism did not affect the peak of HCQ and DHCQ.Conclusion:The concentration of HCQ and DHCQ in breast milk is positively correlated to the dosage. The peak level of HCQ milk is 4 hours after taking the drug. The levels of HCQ and DHCQ at 6 hours are similar as those in the whole blood. It is suggested that patients who take HCQ can feed 4 hours after taking the drug to reduce the HCQ and its active metabolites being absorbed by infants. However, the impact of HCQ on infant safety and gene polymorphism of CYP on milk concentration among individuals needs to be further verified in large sample studies and long-term follow-up.

Objective:To investigate the distribution of blood concentration of cyclosporine (CsA) in patients with autoimmune disease in China, and analyze the effect of genetic polymorphisms of CsA-metabolizing enzymes, transporters and target enzymes on CsA levels.Methods:Steady-state trough blood concentrations (CsA C 0) of 193 patients' were detected by enzyme multiplied immunoassay technique. The genotype of the following sites in the included patients were sequenced by reverse transcription-polymerase chain reaction (RT-PCR): cytochrome P450 (CYP) 3A420230C>T, CYP3A56986A>G, ATP binding cassette subfamily B member 1 (ABCB1)1236C>T, ABCB12677G>T/A, ABCB13435C>T, cytochrome P450 oxidoreductase (POR) 1508 C>T and formyl peptide receptor 1 (FPR1) C>G were sequenced by RT-PCR. The influence of the gene polymorphism of the above-mentioned sites on the blood concentration of CsA was analyzed by using One-way analysis of variance (ANOVA), LSD- t test, Chi-square test. Results:One hundred and ninety-three patients included took CsA. The doses ranged from 75-200 mg/d and the patients' blood concentration distribution span was wide (33.0-313.8 ng/ml). The daily dose ( χ2=21.908, P=0.001) and age( F=4.262, P=0.006) had significant effect on the plasma concentration of CsA. ABCB12677G>T/A (rs2032582) gene polymorphism impacted on the unit dose of CsA C 0 (CsA C 0/d), CsA C 0/d [(0.81±0.42) ng·ml -1·mg -1] in wild type (GG) was higher than heterozygous mutant [GT/GA, (0.65±0.30) ng·ml -1·mg -1, P=0.023) and homozygous mutant (TT/AA/TA, (0.66±0.34) ng·ml -1·mg -1, P=0.039). Conclusion:The blood concentration of patients varies greatly among individuals. The Cold of CsA in wild type patients with ABCB12677G>T/A gene is signifficantly higher than that in mutant patients.

Disulfiram (DSF) has been widely used in clinical treatment of alcoholism.To date,in vivo and in vitro experiments have demonstrated that DSF has strong anti-cancer activity and could improve patient's survival,and the underlying mechanism has been elaborated.In addition,it was reported that,during radiotherapy,DSF could protect normal tissue and cells meanwhile enhance the radiosensitivity of tumor cells by forming complexes with copper ions,suppressing cancer stem cells and inhibiting ubiquitin-proteasome system activity in cancer cells.This review summarizes the completed and ongoing clinical trials of disulfiram,and its anti-tumor mechanisms and advances in radiation biology.