Tacrolimus is an widely used immunosuppressant in organ transplant patients for anti-rejection,and the quality of life and survival rate are greatly enhanced.At present,a growing number of scholars concerned with drug interactions of Western medicine and tacrolimus.However,the impact of planta medica on it was rarely systematically overviewed.This article explored the interaction of planta medica and tacrolimus.

AIM: To study the pharmacokinetics of magnesium isoglycyrrhizinate (MgIG),which was diluted by 5%glucose injection in a total volume of 250 mL, after a single and multiple intravenous dose in 10 healthy volunteers.　METHODS: MgIG 100 mg once daily for 9 d in the multiple-dose regiment. Plasma MgIG concentrations are measured using high performance liquid chromatography (HPLC). Waters HPLC instrument was used with the Hypersil ODS2 C18 (5 μm, 300 mm×4.6 mm) column. The mobile phase was composed of 0.23 mol·L-1 phosphate buffer (pH=7.4):acetonitrile (79∶21).Flow rate was 1.0 mL·min-1 and column temperature was maintained at 40°C. The UV detector was set at 250 nm. The concentration time curves of MgIG were fitted to a two-compartment open model.　RESULTS: The pharmacokinetic parameters obtained from the single-dose study were as follows: cmax=(29±s 4) mg·L-1;t(1)/(2)α=(1.72±0.27) h;t(1)/(2)α=(23±3) h and AUC0-72=(448±75) mg·h·L-1. The steady-state pharmacokinetic parameters were: cssmin=(13±3) mg·L-1;cssmax=(42±6) mg·L-1;cav=(21±4) mg·L-1;t(1)/(2)α=(1.6±0.4) h;t(1)/(2)β=(24±4) h and AUCss0-24=(513±108) mg·h·L-1.CONCLUSION:The distribution and elimination rate of MgIG were not changed after multiple intravenous administration.

The occurrence and development of malignant glioma are closely related to abnormal overexpression and activation of receptor tyrosine kinase (RTK) signal transduction pathways.Targeted therapeutic drugs such as RTK inhibitors,RTK downstream signaling pathway inhibitors and multi-target inhibitors can targeting treat malignant glioma at molecular level,some of which have been investigated in clinical trials and achieved good therapeutic effects.

Objective To assess the safety and tolerance of single-dose and continuous intravenous drip of Xuesaitong saline injection in Chinese volunteers,thus to establish the effective clinical dosage.Methods Thirty-one healthy volunteers were randomized into 4 single-dose groups(100,200,400 and 600 mg respectively)and a multiple-dose group(400 mg,qd ? 14 d).Subjective symptoms,objective signs,vital signs including blood pressure,heart rate,respiration were observed,and routine blood tests,routine urine tests,hepatic function,renal function,clotting function,electrocardiogram were monitored after medication.Results In the single-dose groups,there were no abnormal findings in the vital signs and the lab examinations 0h,1h,8h,24h after medication.Dizziness without association with Xuesaitong occurring in one volunteers of the 200 mg group.It could subside after taking a rest.In the multiple-dose group,no significant changes were found in the vital signs and the lab examinations 4 d,8 d,12 d,15 d after the first dosing.Rash occurred in 2 volunteers,being considered potentially related to the drug and disappearing in one week.Conclusions Xuesaitong is safe at a dose of 100 ~ 600 mg in a single administration or at a dose of 400 mg once day for 14 days for male or female Chinese volunteers,400 mg being suggested for the clinical use.However,Further studies are needed to evaluate the safety of xuesaitong in the target population and allergic reaction should be observed.

Aim To study the pharmacokinetics of faropenem sodium for injection after a single and multiple intravenous dose in 12 healthy volunteers.Methods Multiple-dose regiments used 12-hour dosing intervals for 5 doses.Plasma and urine faropenem sodium concentrations were measured using high-performance liquid chromatography.The concentration-time curves of faropenem sodium were fitted to a two-compartment open model.The excretion data in urine were disposed by the method of excretion rate in urine.Results The pharmacokinetic parameters obtained from the single-dose study were as follows: C_(max) =(45.20±8.73) mg·L ~(-1); T_(1/2α) =(0.401±0.096) h; T_(1/2β) =(1.419±0.267) h;AUC_(0-12) =(59.216±11.886) mg·h·L~(-1) .The steady-state pharmacokinetic parameters were: C ss min =(0.03±0.02) mg·L~(-1) ; C ss max =(44.60±9.08) mg·L~(-1) ; C_(av)=(4.939±1.048) mg·L~(-1) ; T_(1/2α) =(0.340±0.105) h; T_(1/2β) =(1.257±0.173) h;AUC~(ss)_(0-12) =(59.268±12.571) mg·h·L~(-1) .The amount of cumulative recovery of faropenem sodium in urine for single and multiple dose within 12 h was(30.48±12.77)% and (40.55±17.53)%, respectively.The pharmacokinetic parameters in urine of the single-dose study were: T_(1/2) =(0.993±0.088) h, K_e=(0.227±0.097) h~(-1) .The steady-state pharmacokinetic parameters in urine were: T_(1/2) =(1.085±0.069) h, K_e=(0.296±0.136) h~(-1) .Conclusions The distribution and elimination rates of faropenem sodium for injection are not changed after multiple intravenous administrations.Effective concentrations in vivo can be achieved after the repeated administration with 400 mg twice a day regiment.The dosing schedule can be recommended.

OBJECTIVE:To evaluate the safety and tolerance of magnesium isoglycyrrhizinate(MgIG)injection in Chinese healthy volunteers,and provide safe and utility dosage scheme.METHODS:36healthy volunteers were randomly divided into4groups,each group administered respectively with single-dose intravenous infusion of100,200,300mg of MgIG and mul?ti-dose intravenous infusion of200mg of MgIG,qd for7consecutive days.Clinical symptoms,vital signs,electrocardiograms,routine blood and urine tests,as well as hepatic and renal function were observed before and after IV infusion of MgIG.RESULTS:In single-dose IV infusion of MgIG groups,the vital signs and laboratory indices did not change in the subjects immediately after or at1h,8h,24h after administration,as compared with before,while in multi-dose constant intravenous infusion group,the vital signs and laboratory indices at4days and8days after administration were in the normal range,as compared with before.CONCLUSION:Tolerance of healthy subjects to MgIG is good,and daily dosage of100mg to200mg is recommended for clinical use.

AIM:To develop a high performance liquid chromatography -mass spectrometry method for the determination of ?-Lipoic acid in plasma,to study the pharmacokinetics of ?-Lipoic acid and evaluate the bioequivalence of two preparations in healthy subjects. METHODS:A single oral dose of 200 mg ?-Lipoic acid capsules and tablets was given to 22 healthy male volunteers according to an open randomized 2 way crossover design. Plasma concentrations of ?-Lipoic acid were determined by HPLC-MS method. The pharmacokinetic parameters and relative bioavailability were calculated to evaluate the bioequivalence of the two preparations. RESULTS:The pharmacokinetic parameters of the two products were as follows:tmax were (16?4) and (20?20) min,?max were (1490?359) and (1537?290) ng/mL,AUC0-t were (59559?18456) and (58210?15080) ng?mL-1?min,AUC0-∞ were (60068?18556) and (58634?15126) ng?mL-1?min,respectively. The relative bioavailability of AUC0-t and AUC0-∞ were (102.97?18.28)% and (103.09?18.26)%. CONCLUSION:The result demonstrated that two formations are bioequivalent by statistical analysis of variant,two one-side t-test and 90% confidential interval.

Aim To investigate the pharmacokinetics of intravenous injection of magnesium isoglycyrrhizinate in single dose in Chinese healthy volunteers.Methods 9 healthy volunteers received magnesium isoglycyrrhizinate injections in single dose of 100,200,300 mg respectively.The concentrations of magnesium isoglycyrrhizinate in plasma at different time were assayed with HPLC-UV method.The pharmacokinetic parameters of magnesium isoglycyrrhizinate injections were calculated with program 3P87.Results It was found that the plasma concentration-time curves of the preparetion fitted two-compartment model.The main pharmacokinetic parameters were as follows: C_(max) were(28.79?3.54),(67.56?8.84) and(99.28?17.57) mg?L~(-1);T_(12?) were(1.72?0.27),(1.46?0.35) and(1.13?0.33) h;T_(12?)were(23.10?3.30),(23.95?4.72) and(24.25?4.12) h;V_d were(3.332?0.471),(2.921?0.382) and(2.921?0.622) L;CL were(0.209?0.041),(0.186?0.048) and(0.166?0.039) L?h~(-1);k_(10) were(0.063?0.012),(0.064?0.016) and(0.057?0.009) h~(-1);AUC_(0-72) were(448.68?75.06),(1015.29?225.14) and(1688.42?367.44) mg?h ?L~(-1).Conclusion The pharmacokinetics of the drug in the dosage range of 100～300 mg in human body approximately fit linear dynamic features.Compared with glycyrrhizic acid and other glycyrrhizinate salts,magnesium isoglycyrrhizinate is eliminated more slowly.This is beneficial to the treatment of chronic hepatitis.

Objective:To observe the occurrence of ADRs in a hospital and analyze its correlative factors.Meth- od:131 ADR cases collected in a hospital in 2006 were categorized statistically analyzed.Result:121 of the 131 ADR ca- ses were induced by chemical drugs,and the other 10 cases,induced by the traditional Chinese drugs.In the 121 ADR ca- ses induced by chemical drug,the most were induced by intravenous injection,which occupied 49.62%.Antimicrobial drugs were the first category of drugs to cause ADRs,totaling 77 cases from 42 drugs.ADR most commonly manifested themselves in the injury of skin and appendents,which accounted for 52.89%(64 cases).There were 10 comparatively serious ADR cases.Conclusion:The occurrence of ADRs was related to many factors,such as administration route and drug varieties.ADRs monitoring and publicizing of ADRs knowledge should be strengthened so as to lessen and avoid the occurrence of ADRs.

Aim To provide references for clinical trials dose and rational drug use by evaluating mitochondrial toxicity of bentysrepinine on HepG2 cells.Methods Mitochondrial toxicity of bentysrepinine on HepG2 cells was cmomprehensively evaluated by measuring proliferation inhibition rate, lactic acid content in culture supernatant, reactive oxygen species(ROS) content, mitochondrial membrane potential (MMP) variation and the activity of mitochondrial respiratory chain complex enzymes Ⅰ to Ⅳ.Results The half inhibitory concentration of bentysrepinine of HepG2 cells was 359 μmol·L-1.Compared with the control group, bentysrepinine could reduce the MMP, raise the level of lactic acid, increase the content of ROS and lower the activity of mitochondrial respiratory chain complex enzymes Ⅰ to Ⅲ with the concentration of 400 μmol·L-1(196 mg·L-1), showing an obvious mitochondrial toxicity.Compared with lamivudine and adefovir dipivoxil, bentysrepinine exerted no influence on indexes above with the same concentration 100 μmol·L-1.Conclusions Bentysrepinine shows an obvious mitochondrial toxicity on HepG2 cells with the concentration of 400 μmol·L-1.This mitochondrial toxicity is not presented with the concentration of 200 μmol·L-1.It shows that the safety range of bentysrepinine about mitochondrial toxicity is relatively wide.The test plays a guiding role in clinical trial dose design as well as clinical treatment.