Determination of Rhodamine 123 in Rat Plasma by High Performance Liquid Chromatography / 医药导报

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.

Effects of Berberine on In Vivo Pharmacokinetics of Midazolam and Its Metabolite in Rats / 医药导报

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.

Ressearch on Risk Factors of Adverse Reactions Caused by Tacrolomus in Renal Transplant Recipients / 中国药师

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.

Association of Gene Polymorphism with Individualized Tacrolimus Dosage Regimen in Renal Transplant Recipients / 医药导报

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.

Treatment of advanced neuroendocrine tumors with ~(90)Y-DOTATATE / 中华核医学杂志

Objective To evaluate the effcacy and side effects of [~(90)Y-1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA)~0,Tyr3]octreotate (~(90)Y-DOTATATE) combined with lysine as a renal protective agent.Methods Twenty-five patients with advanced neuroendocrine tumors were confirmed as somatostatin receptor subtype-2 (SSTR2)-positive by somatostatin receptor scintigraphy (SRS).Each patient received 1-5 cycles of treatment and the interval between two cycles of treatment was 6-9 weeks.~(90)Y-DOTATATE was administered intravenously within 30 min.Lysine was injected before and after the administration of ~(90)Y-DOTATATE.After each treatment cycle.the side effects were assessed according to National Cancer Institute Grading Criteria(NCIGC).The etticacy was evaluated by the WHO criteria 8 weeks after the last treatment.Results Pattial remission was found in 1 patient (4%).minor response in 3 patients(12%),stable disease in 16 patients (64%)and tumor progression in 5 patients (20%).Two patients suffered from renal functional injuries and 3 patients developed leukocytopenia.Three patients showed nausea while another 3 patients presented vomiting.Conclusions ~(90)Y-DOTATATE in association with lysine may be a promising treatment method for the patients with metastatic and inoperable neuroendocrine tumors.More research work may be directed to reduce renal injury.

Patterns and characteristics of brown adipose tissue uptake of 18F-FDG positron emission tomograph/computed tomography imaging / 中国医学科学院学报

<p><b>OBJECTIVE</b>To characterize the brown adipose tissue (BAT) uptake of 18F-FDG on positron emission tomography (PET)/computed tomography (CT) imaging.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 1 080 patients who received all whole-body PET/CT studies in Peking Union Medica College Hospital from July 2008 to February 2009.</p><p><b>RESULTS</b>Forty-one patients (3.8%) were identified to be with BAT uptake, especially during cold seasons. BAT uptake was mostly observed at the neck regions symmetrically (n = 39), and was also seen at paravertebral junctions (n = 30), perinephric regions (n = 21), and mediastinum (n = 10). Patients with BAT uptake had significantly lower male/female ratio (P = 0.0030), younger age (P = 0.0001), and less body mass index (BMI) (P = 0.0415). Three patients with high BAT uptake underwent repeat PET/CT scans 3-7 days later. By keeping warm and full relaxation, BAT uptake disappeared in 2 cases and dramatically decreased in the other case.</p><p><b>CONCLUSIONS</b>BAT uptake commonly occurs during cold seasons in Beijing, especially in young females with low BMI. It usually has specific patterns, and can be avoided or remarkably reduced by asking the patients keep warm and full relaxation a few days before the scanning.</p>

Preoperative evaluation of liver function using 99mTc-diethyl iminodiacetic acid based on single photon emission computed tomography / 中国医学科学院学报

<p><b>OBJECTIVE</b>To establish a three-dimentional liver function evaluation system using 99mTc-diethyl iminodiacetic acid (99mTc-EHIDA) scintigraphy based on single photon emission computed tomography (SPECT).</p><p><b>METHODS</b>Totally 16 patients with liver lesions were divided into cirrhosis group and non-cirrhosis group. SPECT was performed 2 days before operation and 5 days after operation. Serum liver functions were examined on the same day of scintigraphy. SPECT images of areas of interest of heart and liver were aquired. Time of the peak of EHIDA density in liver (Tpeak), five-minutes heart liver index (HLI5), blood clearance index (HH15), receptor index (LHL15), and the predictive values were calculated.</p><p><b>RESULTS</b>Tpeak was not significantly different between two groups, while HLI5, HH15, and LHL15 were significantly different (P = 0.033, P = 0.001, and P = 0.005). HLI, and LHL15 were significantly correlated with preoperative total protein and prealbumin levels (P = 0.003, P = 0.015, P = 0.022, P = 0.038) and post-operative prealbumin (P = 0.037, P = 0.042). The predictive values of HLI5 and LHL15 correlated well with postoperative HLI5 and LHL15 (r = 0.675, P = 0.016; r = 0.629, P = 0.028).</p><p><b>CONCLUSION</b>The three-dimentional liver function evaluation system using 99mTc-EHIDA based on liver SPECT may facilitate the further studies of risks of liver surgery.</p>