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OBJECTIVE To explore the appropriate dosing regimen of meropenem in the elderly with renal insufficiency. METHODS The meropenem population pharmacokinetics of the two-compartment model of elderly patients were applied for Monte Carlo simulation. The model included the effect of renal function on the parameters. The designed dosages were 0.5， 1， 2 g； the administration modes included intravenous injection （lasting for 6 min） and intravenous drip （0.5， 3 h）； the administration frequencies were q12 h， q8 h. A total of 18 dosing regimens were designed. The probability of target attainment of %fT＞4MIC≥40% and Cmin≤27.5 mg/L were calculated respectively to optimize the dosing regimen. RESULTS For elderly patients with creatinine clearance （CLcr） ≤40 mL/min， when the minimum inhibitory concentration （MIC） was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous drip 0.5 h， q12 h”“ 1 g， intravenous injection， q12 h”. When the MIC was equaled to 2 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h”“ 1 g， intravenous drip 0.5 h， q12 h”. When the MIC was equaled to 4， 8 mg/L， the suggested dosing regimens were “1 g （or 2 g）， intravenous injection， q8 h”. For elderly patients with CLcr equal to 50 mL/min， when the MIC was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h“”1 g， intravenous injection， q12 h”. When the MIC was equal to 2， 4， 8 mg/L，the suggested dosing regimens were“0.5 g （or 1 g， or 2 g）， intravenous drip for 0.5 h， q8 h”. The appropriate dosing regimens of all the above protocols were above 96.6%. In the dosing regimen of “2 g，intravenous injection or intravenous drip 0.5 h， q8 h”， Cmin＞27.5 mg/L occurred in 40 times among the 1 000 times of simulation， indicating adverse reactions of the nervous system may occur. CONCLUSIONS For the elderly patients with renal insufficiency， the dosing regimen of meropenem should be adjusted accordingly with CLcr＝40 mL/min as the boundary， and the toxicity of nervous system should be considered at the same time.
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AIM: To build a meropenem population pharmacokinetic model for Chinese elderly through model-based meta-analysis. METHODS: Informations including dosing regimen, sampling times, concentrations, sample size, age, gender, body weight (BW) and creatinine clearance were extracted after the literature were retrieved. The model was built by NONMEM. Stepwise covariate modeling strategy was used for covariates analysis. RESULTS: A two-compartment model was applied to describe meropenem pharmacokinetics. After stepwise covariate modeling, covariates that remained significant in the final model were creatinine clearance (CLcr) on CL and the BW on V
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Objective:To evaluate the effect of anesthesia factor on postoperative outcome in patients undergoing thoracoscopy through a comparison between different analgesic methods.Methods:One hundred patients of both sexes, aged 18-64 yr, with body mass index of 18.5-24.0 kg/m 2, of American Society of Anesthesiologists physical statusⅠ or Ⅱ, scheduled for elective single-hole thoracoscopic surgery, were divided into 4 groups ( n=25 each) using a random number table method: control group (group C), erector spinae plane block (ESPB) group (group E), thoracic paravertebral nerve block (TPVB) group (group T), and ESPB combined with TPVB group (ET group). Before induction of anesthesia, ultrasound-guided nerve block was performed, and ESPB, TPVB, and ESPB combined with TPVB were performed on the affected side in E, T and ET groups, respectively.The mixture of 0.5% ropivacaine 20 ml and dexamethasone 5 mg was injected in T and E groups, and 0.5% ropivacaine 5 ml was injected into the paravertebral space, the needle tip was retracted to touch the transverse bone, and then another 15 ml was injected in group ET.The block plane was detected by acupuncture at 15 min after completion of the nerve block, and successful nerve block was defined as the block plane reaching T 4-6 in the areas innervated by the spinal nerve.Both groups received patient-controlled intravenous analgesia(PCIA) and were admitted to postanesthesia care unit after surgery.Flurbiprofen axetil 50 mg was intravenously injected as rescue analgesic when the visual analog scale(VAS)score was more than 3.Venous blood samples were collected immediately before nerve block operation (T 0), 30 min after operation (T 1), 30 min after tracheal extubation (T 2), and 24 h after operation (T 3) for determination of the concentrations of plasma cortisol and adrenocorticotropic hormone (ACTH) by enzyme-linked immunosorbent assay.The VAS score for cough was recorded at 15 min after tracheal extubation (T 4) and 6, 12, 24 and 48 h after surgery (T 5-8). The patients were followed up at 48 h after surgery.The pressing times of PCIA, consumption of flurbiprofen, and development of nausea and vomiting were recorded. Results:Compared with group C, VAS scores for cough were significantly decreased at T 4-6, the pressing times of PCIA was reduced, and the consumption of flurbiprofen, and incidence of nausea and vomiting and plasma Cor and ACTH concentrations at T 1-2 were decreased in the other three groups ( P<0.05). Compared with group E, VAS scores for cough at T 4, pressing times of PCIA and consumption of flurbiprofen were significantly decreased in T and ET groups ( P<0.05). There was no significant difference in each index between ET group and T group ( P>0.05). Conclusion:TPVB performs better than ESPB and TPVB combined with ESPB in improving the postoperative outcome of patients undergoing thoracoscopy.
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Objective: To study the acute toxicity of Xiaobai capsules in mice after intragastric administration .Methods: The mice were randomly divided into two groups , the treatment group and the control group .The treatment group was given Xiaobai cap-sules by gavage, 3 times daily.The acute toxicity was recorded, and the median lethal dose (LD50) and the maximum dose were deter-mined.Results:The maximum daily dose of Xiaobai capsules was 141.6 g· kg-1(equivalent to 211.3 times of the clinical dose).At the dose, the mice showed no toxicity without death in 14 days or changes in organs after the dissection .Conclusion:Xiaobai capsules have very low acute toxicity in mice after intragastric administration with high security .