Intestinal CYP3A4-mediated biotransformation and active efflux of absorbed drug by P-glycoprotein are major determinants of bioavailability of orally administered drugs. The expression of CYP3A4 and P-glycoprotein in the intestine is not co-ordinately regulated. However, synergistic actions of CYP3A4 and P-glycoprotein in intestinal drug disposition have been confirmed by in vitro and animal studies. Further understanding of this interaction would be potentially useful to improve oral bioavailability of CYP3A4/P-glycoprotein substrates.

OBJECTIVE:The effects of theasinesin on the immune functions of normal and immunosuppressed nice were studied.METHODS:The immunosuppressed mice were induced by cyclophosphamide(15mg/(kg?d)?4d,ip).The immunom_odulatory effects of theasinesin were measured by delayed type hypersensitivity(DTH),phagocytosing function assay of peritoneal macrophage,cleaning charcoal particles method,and HC50 method.RESULTS:Theasinesin(50,100,200mg/(kg?d)?7d)could significantly intensify DTH caused by DNFB.It could also improve phagocytosing function of peritoneal macrophage and increase production of serum hemolysins in mice immunized with SRBC.The ear swelling,K,? and the level of serum hem_olysin that were lowered by cyclophosphamide were also markedly increased by theasinesin.CONCLUSION:Theasinesin has an enhanced effect on immunofuctions of normal mice ans immunosuppressed mice.

Immunosuppressive drugs used in organ transplantation are highly effective in preventing acute rejection. However,the clinical use of the drugs is complicated by the fact that they display highly variable pharmacokinetics and pharmacodynamics among in-dividual patients. The influence of genetic variation on the interindividual variability in immunosuppressive drug disposition,efficacy and toxicity has been explored in recent years. The review summarized all kinds of immunosuppressants and their relationship with ge-netic polymorphisms,including the SNPs of related enzymes about pharmacokinetics and pharmacodynamics,the SNPs of donor and tar-get site. The review focused on the current situation and progress in the related research areas.

Objective:To investigate the correlation of ABCB1 polymorphisms and the synergistic effect of Wuzhi capsules on ta-crolimus. Methods:The ABCB11236C>T(rs1128503), ABCB12677G>T/A(rs2032582) and ABCB13435C>T(rs1045642) genotypes were determined by restriction fragment length polymorphism ( RFLP) analysis. The whole blood levels of tacrolimus in renal transplant recipients were measured by chemiluminescent microparticle immunoassay. Analysis of covariance ( ANCOVA) was per-formed to determine the difference of tacrolimus C0/D among the various groups. Results: Whether co-administeration of Wuzhi cap-sules and tacrolimus or not, tacrolimus C0/D of ABCB11236C>T, ABCB12677G>T/A and ABCB13435C>T genotype and haplo-type was without significant difference. Conclusion:When combined with Wuzhi capsules, ABCB11236C>T, ABCB12677G>T/A and ABCB13435C>T mutation is not associated with tacrolimus C0/D.

Pharmacogenomics does not only bring the connection of genes,medicines and diseases,but also become a powerful tool for clinical pharmacists.Pharmacogenomics is commonly used in clinical practice,especially in the implementation of genetic-test results for guiding rational use of medicines.The genotyping results of genes can provide good individualized medication guidance for patients,which can be confirmed by clinical use of the clopidogrel and warfarin.As a member of the clinical treatment team,clinical pharmacists should take advantage of pharmaceutical and pharmacogenomics information to promote rational use of medicines.

Pregnane X receptor ( PXR) , a member of the nuclear receptor subfamily, plays an important role in the regulation of drug metabolic enzymes and transporters. PXR can regulate the expression of downstream target genes through transforming a large number of exogenous and endogenous chemical substances, and can be activated by a variety of Chinese herbal medicines. The same as PXR, constitutive androstane receptor ( CAR) can participate in the regulation of drug metabolic enzyme CYP450 and become the targets of drug action through combining with exogenous ligands to regulate the expression of CYP2B6, CYP3A4, CYP2C19 and UGT1A1.

Objective:To study the characteristics of the adverse reactions caused by tacrolimus and analyze the risk factors. Methods:Totally 280 cases of renal transplant recipients received standard treatment options were selected from 1997 to 2013 in Wuhan general hospital of Guangzhou military command. The tacrolimus-related adverse reactions and their risk factors were analyzed statistically. Results:Totally 39. 65% of the patients had the tacrolimus-related adverse reactions. The main adverse reactions were hematotoxicity,diabetes mellitus and hyperlipidemia. The univariate analysis showed that age,weight,BMI and treatment course were the suspected risk factors. The multivariate analysis results showed that age,BMI and treatment course were the risk factors of tacrolimus-related adverse reactions. Conclusion:The incidence of tacrolimus-related adverse reactions is relatively high,and if the patient is in advanced age,with poor nutritional status or long-term medication,the probability of adverse reactions will be increased.

Objective:To investigate the effects of schizandrin B on P- glycoprotein by a classical in vitro cell model. Methods:Caco-2 cell model was used as the carrier,and rhodamine 123 and cyclosporin A were employed as the P-gp substrates, the transmembrane transportation of schizandrin B,rodamine 123 and cyclosporin A were detected by HPLC and a liquid scintillation counting assay,and the apparent permeability coefficient and permeability directional ratio were calculated. Results:The bidirectional transportation rates of schizandrin B(20 μg·ml -1 ,40 μg·ml -1 and 80μg·ml-1 )were similar,and showed non-selective difference. Schizandrin B(20-160 μg ·ml -1 )significantly inhibited the BL → AP directional transportation of rhodamine 123 and cyclosporine A in Caco-2 cell model(P < 0. 05) in a concentration-dependent manner. Conclusion:Schizandrin B is a P-gp inhibitor,while it isn’t a P-gp substrate.

Tacrolimus is a novel immunosuppressant used in the treatment of a variety of autoimmune diseases.More and more studies have shown that tacrolimus has a certain therapeutic effect on myasthenia gravis (MG).This article reviews the mechanism,clinical researches,adverse reactions,dosage and clinical evaluation of tacrolimus in the treatment of MG.

Objective:To discuss the ways to deal with adverse drug reactions in pharmaceutical care. Methods:A case of drug-induced kidney injury was provided to analyze the effect of clinical pharmacist on adverse drug reactions. Results and Conclusion:Good quality of pharmaceutical care, such as reliable drug information, is valuable in clinical practice.