Comparison of drug concentrations in blood and gastric lavage fluid before and after gastric lavage:A case report

BACKGROUND Gastric lavage(GL)is one of the most important early therapies to remove unabsorbed toxins from the gastrointestinal tract.However,the details of performing gastric lavage remain to be established.There is controversy in clinical practice regarding individual choice of the timing of GL and its efficiency.CASE SUMMARY We report the case of a young woman who presented to the Emergency Department with drug intoxication for four hours.We used the latest toxicological screening techniques to compare drug concentrations in the patient's blood and gastric lavage fluid before and after gastric lavage.The results confirmed that gastric lavage was effective in reducing drug concentrations in the stomach;a small amount of drug remained in the stomach at the end of gastric lavage.CONCLUSION Gastric lavage is effective in reducing drug concentrations in the stomach,with a small amount of drug remaining in the stomach at the end of gastric lavage.

Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China

BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

Comparisons of drug efficacy and time-effect among magnesium valproate,sustained-release magnesium valproate tablet and depakine chrono for epilepsy An experiment of determining cortical convulsive threshold in rats undergoing electrical stimulation

BACKGROUND： Scholars have investigated the differences in drug metabolism and pharmacodynamics between valproate and its sustained-release tablets only from the angle of pharmaceutical sciences or clinical practice. Whether the fact that differences in drug efficacy and time-effect of different doses of valproate and different types of sustained-release valproate tablets at the same concentration can be quantitatively reflected by determining the changes in convulsive threshold pre- and post-administration in rat models of determining the convulsive threshold developed by direct cortical electrical stimulation remains unclear. OBJECTIVE： This study aimed to compare the drug efficacy and time-effect among magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono in the treatment of epilepsy by determining the convulsive threshold of rat models created by direct cortical electrical stimulation, and human serum drug concentration before and after administration. DESIGN： A controlled observational experiment. SETTING： Research Institute of Epilepsy, Shanxi Medical University. MATERIALS： Adult health male SD rats of clean grade, weighing 200 - 220 g, provided by the Laboratory Animal Center of Shanxi Medical University. The protocol was carried out in accordance with requests from Animal Ethics Committees for guidance. Magnesium valproate （Lot No. 041004） and sustained-release magnesium valproate tablet （Lot No. 050501） were produced in Hunan Xiangzhong Pharmaceutical Co., Ltd. METHODS： This study was carried out in the Laboratory for Epilepsy, Shanxi Medical University between June and August 2005. （1）All the SD rats were created into models for determining cortical convulsive threshold. They were randomly divided into 4 groups with 20 rats in each： magnesium valproate tablet group, sustained-release magnesium valproate tablet group, depakine chrono group and control group. After being modeled, the rats in the first 3 groups were intragastrically administrated with magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono, respectively, while the control group were intragastrically administrated with the same volume of normal saline. （2）Convulsive threshold of each fasting rat was determined 0.5 hour before, and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14 and 24 hours after single administration, separately. （3） Convulsive threshold was determined repeatedly 2 weeks after single administration. Each rat was administrated two times daily successively. Convulsive threshold was determined 0.5 hour before, and 0.5, 2.5, 7 and 12 hours after administration, separately. （4）Hepatic and renal tissues were harvested for pathological examination after 1 month of administration. （5）Nine healthy voluntary medical stuffs were recruited in this study. Written informed consents of experiment were obtained each involved subject. The study was given an approval by the Ethics Committee of Shanxi Medical University. According to the scheme, the 9 volunteers were randomly assigned into 3 groups, in which, volunteers were asked to take magnesium valproate 500 g, sustained-release magnesium valproate tablet 500 g and depakine chrono 500 g, respectively, in the morning under the condition of fasting. Serum drug concentration of each drug was determined by fluorescence polarization immunoassay at different time points. MAIN OUTCOME MEASURES： （2） Rat convulsive threshold after single and repeated administrations. （2）Hepatic and renal pathological examination results. （3） Serum drug concentration in vivo. RESULTS：（4）Rat convulsive threshold after single and repeated administrations： Drug efficacy in the magnesium valproate tablet group reached to a peak level 1 to 2 hours after single administration, and was obviously higher than that in the other groups 1 hour after administration （P 〈 0.05）. Drug efficacy in the sustained-release magnesium valproate tablet group and depakine chrono group both reached to a peak level 7 hours after administration, and was significantly higher than that in the control group （P 〈 0.05）. After repeated administrations, the average peak valley deviation of the convulsive threshold in the magnesium valproate tablet group was 120- 150 μ A, which was 2 and 2.5 times as that in the sustained-release magnesium valproate tablet group and depakine chrono group, respectively. After repeated administrations for 10 times, convulsive threshold was increased by 440 μ A in the sustained-release magnesium valproate tablet group, and by 230 μ A in the depakine chrono group in comparison with before administration. （2） Hepatic and renal pathological examination results： No obvious differences in hepatic and renal impairment were found among the 4 groups after I month of administration successively. （3） Serum drug concentration in vivo： Serum-drug concentration of magnesium valproate was increased fast and reached to a peak level 0.5 - 2 hours after administration, remained at a relatively stable level 2 - 4 hours after administration, and then was slowly decreased. The drug efficacy of sustained-release magnesium valproate tablet and depakine chrono was slowly released 1 - 6 hours after administration, reached to a peak level at about 7 hours, and could last for about 16 hours. CONCLUSION： Magnesium valproate has a rapid onset and offset of action. Sustained-release magnesium valproate tablet has a slow onset but long duration of drug efficacy. Depakine chrono can be easier to be absorbed than sustained-release magnesium valproate tablet, but its long-term effect on improving the convulsive threshold is inferior to sustained-release magnesium valproate tablet.

Synergistic Effects of 18β-glycyrrhetinic Acid Combined with Antituberculosis Drugs against Mycobacterium tuberculosis

The in vitro antibacterial activities of 18β-glycyrrhetinic acid alone or combined with first-line antituberculosis drugs including isoniazid（INH）,rifampicin（RFP） and streptomycin（SM） against Mycobacterium tuberculosis were detected using MABA method.The minimum inhibitory concentrations（MICs） of18β-glycyrrhetinic acid against M.tuberculosis H37Rv（ATCC 27294） and M.bovis（ATCC 19210） were 50 and 100 μg/m L,respectively.The MICs of two clinical drug-susceptible isolates and six drug-resistant isolates were 25-50 and 100-200 μg/m L,respectively.As 18β-glycyrrhetinic acid combined with INH,RFP and SM,they exhibited synergistic effects against six drug-resistant isolates,and MICs decreased significantly：MIC of INH decreased by 2-32 folds（FICIs 0.125-0.375）;MIC of RFP decreased by 4-8 folds（FICIs 0.240-0.490）;MIC of SM decreased by 4-16 folds（FICIs 0.165-0.460）.Traditional medicine monomer had low cytotoxicity on normal cell BHK-21 and could restraint SMMC fission.The results showed that 18β-glycyrrhetinic acid combined with anti-TB drugs（INH,RFP and SM） had good antibacterial activity against M.tuberculosis.These findings indicated that 18β-glycyrrhetinic acid might serve as the potential therapeutic compound for future development of anti-TB drugs.

高效液相色谱-离子阱质谱法测定人血浆中的头孢拉定和青霉素G

目前,β-内酰胺类抗生素在临床抗感染药物中占有十分突出的地位[1],但在近年来的药品不良反应报告中,抗生素类药物引起的不良反应也占据了很高的比例,其中有我国生活环境影响、感染性疾病多的客观因素,但病人用药盲目性大、医生用药随意性多的问题也普遍存在.……

Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers

AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori-negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was perform- ed on the day of treatment. Blood samples were also collected after the administration of each drug. RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg.

Determination of Polydatin in Rat Serum and Its Changes by UPLC Method

[Objectives]To establish a UPLC-UV method for the determination of polydatin in the serum of Wistar rats.[Methods]Acquity UPLC BEH shield RP18 column(1.7μm,2.1 mm×100 mm,Waters Corporation,USA)was used as the analytical column,acetonitrile-water(55∶45)was used as the mobile phase,the flow rate was 0.5 mL/min,and the column temperature was 30℃and the detection wavelength was 306 nm.[Results]The linear range of the established serum sample analysis method was 1.0-20.0μg/mL,and the correlation coefficient was r=0.9994;the intraday and interday RSD of Wistar rat serum was less than 3.0%,and the accuracy was higher than 90%.[Conclusions]This method is sensitive,accurate,and rapid.It is suitable for monitoring the concentration of polydatin in serum after intragastric administration,and can also be used for pharmacokinetics and bioavailability studies.

Blood-brain barrier penetration of cefepime after neurosurgery

Background It has been confirmed that the concentration of cefepime in cerebrospinal fluid （CSF） could reach the 10% of its concentration in plasma, exceeding the inhibitory concentration to 90% of organisms （MIC90） for common bacteria. However, the blood-brain barrier （BBB） penetration ability of cefepime is still unclear. The aim of this study was to measure the CSF concentration of cefepime in patients after neurosurgical operations, and to determine the penetration of the drug through an incomplete BBB. Methods Eight patients who received ventricular drainage （VD group） and 5 who underwent lumbar puncture drainage （LPD group） were enrolled into this study. Cefepime （2 g） was injected intravenously in 30 minutes after the neurosurgeries. The concentrations of cefepime in the CSF and plasma were measured by high-pressure liquid chromatography （HPLC） at different time points. Results The CSF concentrations of cefepime at different time points in the VD group were significantly higher than those in the LPD group （P〈0.05）. In the VD group, the concentration of cefepime in CSF reached the peak （（22.54±14.06） pg/ml） at 1 to 2 hours after the injection, while in the LPD group at 4 hours （（5.61±3.73） pg/ml）. In both groups, the peak was higher than the MIC90 of most common bacteria in intensive care unit. The ratio of CSF to plasma cefepime concentrations ranged from 0.30 to 2.14 in the VD group and 0.03 to 1.14 in the LPD group. Conclusion After neurosurgeries, CSF concentration of cefepime can reach a therapeutic level. Thus, the drug could be used to prevent and treat postoperative intracranial infection.

Treatment of Leucopenia with Pure Astragalus Preparation──An Analysis of 115 Leucopenic Patiente

This article reports the effects ot pure Radix Astragali preparation (PAP) in treating 115 cas-es of leucopenia. These cases were divided at random into two groups. Group A (58 cases) was treated byhighly concentrated PAP, every 10 ml equal to 15 grams of Radix Astragali (RA) , group B ( 57 cases) wastreated by lowly concentrated PAP, every 10 ml equal to 5 g of RA. The patients took the PAP twice a day,10 ml each time. The course of treatment was 8 weeks tor both groups. The results showed there was an ob-vious increase of the WBC counts in both groups after treatment ( P< 0. 001 ) . The effectiveness in group Awas 82 . 76% , while in group B 47. 37% , they were statistically different ( P< 0 . 01 ) . The total effective rateof tlie 2 groups was 65. 22% . According to the comparison average WBC counts after treatment of group Awas significantly higher than that of group B ( P < 0. 05) . The results were dose-dependent. The author holdsthat RA is an effective drug in treating leucopenia, and increasing the dosage could enhance its effectiveness.