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Pregnant and breastfeeding women are perhaps "the last true therapeutic orphans". Due to dearth of adequate research on certain medications and healthcare providers' poor knowledge of lactational pharmacology, nursing mothers are often ill-advised to give up breastfeeding or unlikely to receive appropriate treatment. Accumulating evidence-based data have shown that most medications are safe for nursing mothers. Besides safety concerns, infant's condition and maternal attitude should also be considered when making treatment decisions. Clear understanding of lactational pharmacology and risk assessment tools in breastfed infants would be beneficial to meet the medical needs of nursing mothers and promote breastfeeding.
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Objective: To investigate the regulation of CYP3A4 and P-gp by berberine hydrochloride ( BBR) via pregnane X re-ceptor (PXR) pathway. Methods: pLKO. 1-PXR vector, a lentivirus plasmid expressing PXR shRNA, was packaged into 293T cells. Human hepatoma (HepG2) cells were infected with the lentivirus and the cell clones stably expressing PXR shRNA were selected by puromycin according to pLKO. 1 vector characteristics. Real-time RT-PCR and Western blot were used to evaluate CYP3A4 and P-gp mRNA and protein in berberine treated HepG2 cells and PXR-silenced HepG2 cells. Results: The PXR expression in PXR silenced cells significantly decreased (P<0.01) when compared with that in HepG2 cells, while there was no significant difference (P >0. 05) in the expression of CYP3A4 and P-gp between the groups. Compared with that in HepG2 cells, the inhibition of berberine on the mRNA and protein expression of CYP3A4 and P-gp in PXR-silenced HepG2 cells was weakened (P<0. 05 or P<0. 01). Conclu-sion: Berberine can regulate the expression of CYP3A4 and P-gp via PXR signaling pathway, while it is not the only one.
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Objective: To investigate the association between ABCC2 gene polymorphisms and cyclosporine-induced liver injury in re-nal transplant recipients. Methods: The renal transplant recipients were divided into the liver injury group and the control group. Five single nucleotide polymorphisms ( rs4919395, rs2804398, rs4148394, rs4148397 and rs3740065) of ABCC2 were detected by high-throughput technique. The genotypes and haplotypes were analyzed between the groups. Results: There were 35 patients and 182 patients respectively in the liver injury group and the control group. No significant differences in alleles and genotypes were found between the groups (P>0. 05), and the SNP haplotypes showed no significant difference between the groups (P>0. 05). Conclusion: There is no association of ABCC2 polymorphisms (rs4919395, rs2804398, rs4148394, rs4148397 and rs3740065) with the liver injury induced by cy-closporine.
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The main components of Schisandra chinensis are γ-schizandrin, schisandrin A,deoxyschizandrin,schisandra B, schisandrol B and so on. Schisandra contains a variety of bioactive ingredients mainly used in clinics and combined with other drugs. Many of the drugs currently used in clinical practice can cause drug-induced liver injury(DILI),which is one of the main adverse drug reactions,therefore,the clinical use of drugs for the prevention and treatment of liver damage is particularly important. In this paper, the effective components of Schisandra chinensis and their related therapeutic effects on DILI were reviewed.
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Tacrolimus is a kind of calcineurin inhibitor ( CNI) , and it is a novel immunosuppressant with similar efficacy to ciclos-porin. This paper reviewed the recent advances in the treatment of refractory nephrotic syndrome in children with tacrolimus, including the comparison of efficacy, dosage, adverse effects and clinical evaluation with the other immunosuppressive agents such as ciclosporin and mycophenolate mofetil in order to provide reference for clinics.
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Objective To establish a sensitive method for the determination of rhodamine 123 (Rh123) in rat plasma by high performance liquid chromatography (HPLC).Methods The plasma samples were extracted by acetonitrile,and then separated on a Hypersil BDS C18 colunm (4.6 mm×100 mm,5 μm) equipped with a guard column kept at 25 ℃.The mobile phase consisted of acetonitrile and phosphate buffer (0.02 mol·L-1,pH4.0) (60:40) and was pumped at a constant rate of 1.0 mL·min-1.The peak was detected using a fluorescence detector set at FLD1A:Ex=485 nm,Em=546 nm.Results In this study,the method was validated for the Rh123 range of 0.1 to 32.0 μg·L-1,and the lower limit of quantitation (LLO Q) was 0.1 μg·L-1.The intra-and inter-day precisions for Rh123 were less than 7%,and the mean recoveries of Rh123 were 87.93%,89.03%,86.11% at low,mid,and high concentrations,respectively.Conclusion A simple,rapid and reproducible HPLC method was developed for the determination of Rh123 in rat plasma,which was an applicable method in modeling and description of the possible pharmacological interactions between the medicines and P-glycolprotein transporter.
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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.
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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.
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Objective To investigate the influence of deoxyschizandrin (Deo) on P-glycoprotein (P-gp).Methods The effect of P-gp on Deo (20,40,80 μg·mL-1) was studied in the Caco-2 cell model in vitro,and the apparent permeability coefficient (Papp) of Deo (20-160 μg·mL-1) on a P-gp substrate,rhodamine123 or cyclosporine A,was calculated.Healthy male Sprague-Dawley rats were randomly divided into five groups:blank control group,verapamil group,low-,medium-and high-dose Deo group (8 rats in each group).Rats in the low-,medium-and high-dose Deo group were intragastrically administered once daily with Deo at 8,16 and 32 mg·kg-1 for 3 consecutive days,while rats similarly received gavagewith verapamil (4 mg·kg-1) in the verapamil group and equal volume of purified water in the blank control group.Thirty minutes after the rats were treated with their respective drugs,rhodamine123 (5 mg· kg-1) was orally administrated.Then the pharmacokinetic profiles of rhodamine 123 were analyzed to evaluate the inhibitory ability of Deo on P-gp in vivo.Results The bidirectional transport rates of Deo (20,40,80 μg·mL-1) were similar,with non-selectivity.Deo (20-160 pg·mL-1)significantly inhibited the basolateral→apical(BL→AP) directional transports of rhodamine 123 and cyclosporine A in Caco-2 cell model (P ＜ 0.05) in a concentration-dependent manner.And Deo (8-32 mg· kg-1) also dose-dependently decreased the peak concentrations (Cm.) and the area under the plasma concentration-time curve (AUC0-t) of Rho123.Conclusion Deo can inhibit P-gp in vitro and in vivo,but it is not a P-gp substrate.
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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.
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OBJECTIVE:To investigate the association of synergistic effects of Wuzhi capsules on tacrolimus with CYP3A5*3 (6986A>G,rs776746) gene polymorphisms. METHODS:One hundred and severty patients underwent renal transplantation receiving tacrolimus maintenance therapy after surgery were selected from our hospital during Jan. 1997-Dec. 2015,and then divided into Wuzhi capsules(+)group(74 cases)and Wuzhi capsules(-)group(96 cases)according to the use of Wuzhi capsules. Both groups received tacrolimus+mycophenolate mofetil+prednisone;Wuzhi capsules (+)group was additionally given Wuzhi capsules,one capsule each time,bid,for more than 12 months. Trough concentration of tacrolimus was detected by CMIA 0,1,3,6,12 months after medica-tion,and the blood concentrations(C0/D)were calculated at different time points after correcting daily dose. CYP3A5*3 gene polymor-phisms was detected by PCR-RFLP. The association of C0/D value with gene polymorphism was investigated by analysis of covariance. RESULTS:Among 170 patients,there were 65 cases of CYP3A5 GG genotype,83 cases of AG genotype and 22 cases of AA geno-type;genotype frequencies were 38.2%,48.8% and 12.9%,which was in line with Hardy-Weinberg balance (P>0.05). There was statistical significance in the distribution frequencies of GG,AG+AA genotype between Wuzhi capsules(+)group and Wuzhi capsules (-)group (P0.05). CON-CLUSIONS:Wuzhi capsules can increase C0/D of tacrolimus in CYP3A5*3 AG+AA genotype,but have no significant effect on C0/D of tacrolimus in GG genotype;CYP3A5*3 genotype should be considered when using Wuzhi capsules as synergist of tacrolimus.
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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.
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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.
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Objective To examine the effect of berberine hydrochloride ( BER ) on the pharmacokinetic profiles of midazolam,a substrate of CYP3A,in rats. Methods The rats were intragastrically given different doses of BER (50,100, 200 mg?kg-1) or ketoconazole (75 mg?kg-1) for 10 days.Single-pass duodenum perfusion of 20 mg?kg-1 MDZ was performed and the inguinal artery was cannulated for blood sampling.Plasma concentrations of MDZ and 1'-OH-MDZ were analyzed by high performance liquid chromatography ( HPLC) with the CYP3A inhibitor ketoconazole serving as positive control. Results BER (50,100,200 mg?kg-1) and ketoconazole (75 mg?kg-1) could significantly increase the AUC(0-t),AUMC(0-t)and Cmax of MDZ in a dose-dependent manner ( P<0.05) ,and reduce the clearance rate ( CLz ) of MDA and its apparent volume of distribution in the body ( Vz ) ( P<0. 05). But they failed to dramatically affect the half-life ( t1/2z ) and the peak time ( tmax ) of MDZ. Additionally,BER ( 100,200 mg?kg-1 ) and ketoconazole ( 75 mg?kg-1 ) could significantly dose-dependently decrease the AUC(0-t),AUMC(0-t)and Cmaxof 1'-OH-MDZ,and profoundly increase the CLz,tmax and Vz of 1'-OH-MDZ (P<0.05),but they had no remarkable influences on the t1/2z.The ratio of AUC(1'-OH-MDZ)/AUC(MDZ) was decreased with the increase of BER concentration. Conclusion BER can inhibit the in vivo metabolism of MDZ in a dose-dependant manner, which is associated with the suppression of the activity of CYP3A.
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Objective To offer a theory that supports the individualized tacrolimus dosage regimen by retrospectively investigating the influences of gene polymorphism and other clinical factors on tacrolimus concentration in renal transplant recipients. Methods A total of 280 renal transplant recipients were genotyped for CYP3A4?5, CYP3A4?6, CYP3A4?18B, CYP3A5?3, MDR1 1236C>T, MDR1 2677G>T/A, MDR1 3435C>T polymorphisms by PCR followed by restriction fragment length polymorphism (RFLP) analysis.PXR 6bp deletions (rs3842689) genotypes were determined by Allelic Special-Touch down PCR.Correlation between gene polymorphisms and tacrolimus concentrations was analyzed. Results The mutation frequency of CYP3A4?18B, CYP3A5?3, MDR1 1236C>T, 2677G>T/A, 3435C>T and PXR rs3842689 in the renal transplant recipients was 29.11%, 69.29%, 43.57%, 49.64%, 36.43% and 26.07%, respectively.Multiple regression analysis showed that, CYP3A5?3 and red blood cell count were associated with the value of C0/D of FK506, the best regression model was:D=C0/(-60.445 +95.777×CYP3A5 +34.938×RBC), and the equation could explain 38.8% of tacrolimus individual differences. Conclusion Gene polymorphism of CYP3A5?3 and red blood cell count may be responsible, in part, for the large interindividual variability of FK506 dose and concentration.
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Objective:To investigate the effects of HLA-B?1502 genetic polymorphism on cyclosporine( CsA)-induced liver injury in Chinese renal transplant recipients. Methods:HLA-B?1502 genotypes were determined by polymerase amplification chaln reaction of sequence-specific primers( PCR-SSP) in a total of 339 renal transplant recipients receiving CsA. All the subjects were divided into the CsA-induced liver injury group, non-CsA-induced liver injury group and the control group according to the liver injury occurrence. Results:In the 339 renal transplant recipients, the frequency of HLA-B?1502 mutation allele was 22. 64%. The distribution frequen-cy of HLA-B?1502 mutation allele had no significant difference among the three groups. There were no significant differences in the clinical characteristics of HLA-B?1502 genotypes among three groups(P>0. 05). Conclusion: No association is observed between HLA-B?1502 genetic polymorphism and cyclosporine-induced liver injury in Chinese renal transplant recipients.
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Objective: To establish an HPLC-fluoremetry method for determination of the plasma concentration of mycophenolic acid ( MPA) in renal transplantation patients. Methods:The sample was subjected to precipitate proteins using acetonitrile, and the supernatant (20 μl) was used for the sample injection and determination on a Hypersil BDS C18 (250 mm × 4. 6 mm, 5 μm) column with temperature at 25℃. The mobile phase consisted of acetonitrile-methanol-0. 2 mol·L-1 dipotassium hydrogen phosphate buffer (pH=9. 0)( 18∶2∶80)with the flow rate of 1. 0 ml·min-1. The excitation wavelength (Ex) was 342 nm and the emission wave-length ( Em) was 425 nm. Results:The endogenous plasma impurities and drug combinations had no interference with the determina-tion. The calibration curve was linear over the range of 0. 25-50. 00 mg·L-1(r=0. 999 7), and the lower limit of quantification was 0. 25 mg·L-1 . The mean methodological recovery was 99. 12% and the mean extraction recovery was 93. 27%, the intra-day RSD was less than 2% and the inter-day RSD was less than 6%. Totally 10 cases of renal transplantation patients were with mycophenolate mofetil at the dose of 0. 5-1. 75 g·d-1 , and MPA in plasma was within the range of 0. 43-21. 58 mg·L-1 . Conclusion:The method is rapid, sensitive, accurate and convenient, which can be used in the quantitative determination of plasma concentration of MPA in re-nal transplantation patients.
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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.
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OBJECTIVE:To investigate the effect of clinical pharmacist intervention on prophylactic application of antibiotics in cardiothoracic surgery. METHODS:Medical records of patients underwent cardiothoracic surgery were collected from our hospi-tal during Mar. to Apr. in 2014 (before intervention) and during Jun. to Jul. in 2014 (after intervention). Those were divided into pre-intervention group(n=115)and post-intervention group(n=119). The prophylactic application effect of antibiotics was com-pared before and after intervention. RESULTS:After intervention,the rates of prophylactic application were decreased significantly from 96.5% to 72.3%;the rationality rate of antibiotics selection was improved significantly from 27.9% to 94.2%;The course of prophylactic medication decreased significantly from(5.4±2.8)days to(2.3±1.8)days;the difference had statistical significance before and after intervention(P<0.01). The postoperative infection rate was decreased from 13.0% to 5.9%,the difference had no statistical significance(P=0.074). The average hospitalization time,average drug costs,and average hospitalization expenses were decreased significantly,the difference had statistical significance(P<0.05 or P<0.01). CONCLUSIONS:Clinical pharmacist inter-vention to prophylactic application of antibiotics in cardiothoracic surgery can control the infection effective and guarantee reason-able and safe use of drugs during perioperative period.
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Objective:To evaluate the effect of continuing intervention on prophylactic application of antibiotics in sterile operation in urology department by clinical pharmacist to provide reference for the clinical prophylactic application of antibiotics. Methods:All cases of discharged patients underwent sterile operation in urology department of our hospital from July 2010 to June 2014 were divided into three groups according to the intervention time and methods: non-intervention group(n=141), stage Ⅰ intervention group(n=139), stage Ⅱ intervention group (n=162) and stage Ⅲ intervention group (n=137). The prophylactic application of antibiotics was statistically analyzed. Results:After the continuing intervention, the prophylactic application rate of antibiotics in the three inter-vention groups was decreased significantly from 100% before the intervention respectively to 34. 5%,18. 5% and 14. 6% after the in-tervention (P<0. 01). The rationality rate of prophylactic application was improved significantly from 36. 9% before the intervention respectively to 58. 3%, 63. 3% and 85. 0% after the intervention (P<0. 01). The course of prophylactic application was decreased significantly from (138.2 ±31.6)h respectively to (89.9 ±48.0)h,(72.8 ±32.5)h and(45.1 ±29.5)h (P<0.01) and the post-operative infection rate was decreased from 2. 8% respectively to 2. 1%,1. 8% and 1. 4%. Conclusion:The pharmaceutical interven-tion is feasible and valid to improve the rational prophylactic use of antibiotics in urological surgery.