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OBJECTIVE To investigate the effects of individualized dosing regimen on blood trough concentration of vancomycin and renal function in critically ill patients. METHODS According to relevant guidelines and the results of Vancomycin Calculator， clinical pharmacists formulated an individualized dosing regimen of vancomycin including loading dose and maintenance dose for critically ill patients based on the two independent variables of body weight and creatinine clearance rate. Using the method of retrospective study， patients who were admitted to the department of intensive care unit （ICU） of the Second Affiliated Hospital of Guangzhou Medical University and used the regimen from July 2018 to December 2021 were selected as the trial group， and patients who were treated with vancomycin and received blood drug concentration monitoring in ICU from January 2015 to June 2018 were recruited in the control group. The difference in trough concentration distribution and the incidence of acute kidney injury （AKI） after medication were compared between the two groups， the change of serum creatinine before and after medication in the trial group was analyzed. RESULTS Totally 197 patients were included in the trial group and 144 patients were in the control group. There was no significant difference between the two groups in the clinical information （gender， age， body weight， acute physiology and chronic health evaluation Ⅱ score， the proportion of patients with renal insufficiency， etc.） （P＞0.05）. The proportions of major infection sites （including lung， urinary， abdominal， blood and central nervous system） and treatment type （target or empirical treatment） also had no significant difference between the two groups （P＞0.05）. There was no significant difference in the attainment rate of ideal trough concentration （15-20 μg/mL） and the proportion of patients with trough concentration ＞20 μg/mL between the two groups （P＞0.05）， while the attainment rate of target trough concentration （10-20 μg/mL） and the proportion of patients with trough concentration ＜10 μg/mL were significantly different between the two groups （P＜0.05）. The attainment rate of target trough concentration in patients with chronic renal insufficiency in trial group was significantly higher than that in control group （P＜0.05）. There was no significant difference in the incidence of AKI and vancomycin-associated AKI between the two groups （P＞0.05）. In the trial group with medication duration ≥7 days ， the level of serum creatinine on the 7th day of treatment was increased significantly， compared with that on the 3rd day of treatment （P＜0.05）. CONCLUSIONS This individualized dosing regimen can improve the attainment rate of target trough concentration of vancomycin in critically ill patients， especially those with chronic renal insufficiency， during the first standardized monitoring， and not increase the risk of renal injury compared with previous empirical medication.
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AIM: To design and implement personalized dosing regimens of trastuzumab and pertuzumab for an Asian patient with early breast cancer. METHODS: Trastuzumab and pertuzumab are important therapeutics for patients with HER2-positive breast cancer. Despite the similar pharmacokinetics (PK), their recommended dosing regimens differ: pertuzumab dosing is fixed whereas trastuzumab dosing depends on body weight; the dosing frequency is once every three weeks for pertuzumab but includes both once every week (QW) and once every three weeks (Q3W) for trastuzumab. A practicing physician has limited choices for dosing regimens when using the drugs in combination with chemotherapies. Besides convenience in drug administration, efficacy and safety as responses to the drug must be examined as part of studying dose-exposure-response relationship, which is the basis for deciding a dosing regimen. To understand the dose-exposure-response relationship of an individual patient, we reviewed literature on population PK analyses. The associated PK-covariate relationships including influential covariates such as disease status and demographics (e.g., body weight) that informed the patient's underlying dose-exposure-response relationships. Safety and efficacy factors essential for choosing appropriate dosing regimens were also considered - minimal target concentrations, higher adverse event rates in Asian patients, as well as administration convenience. RESULTS:Based on a thorough review of population PK and PK-covariate relationships of pertuzumab and trastuzumab, an individualized dosing regimen of once every two weeks (Q2W) was selected as the treatment option and implemented for this patient. CONCLUSION: The design of an individualized dosing regimen requires the knowledge of individualized dose-exposure-response relationships, and population analysis is an ideal tool for understanding the individualized dose-exposure-response relationships.
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@#AIM: To compare the difference of short-term efficacy of the intravitreal injection of conbercept(IVC)1+PRN and 3+PRN in the treatment of macular edema(ME)secondary to branch retinal vein occlusion(BRVO).<p>METHODS:In this prospective, randomized, and comparative study, 40 patients who were diagnosed as ME secondary to BRVO were divided randomly into 3+PRN group(<i>n</i>=22)and 1+PRN group(<i>n</i>=18). Best-corrected visual acuity(BCVA), central macular thickness(CMT)and mean injection times were compared between two groups in 6mo follow-up period. Baseline predictors of visual acuity(VA)were also investigated.<p>RESULTS: After treatment of 6mo, in the 3+PRN group, the BCVA improved from 0.86±0.22 to 0.41±0.12 and CMT decreased from 517.4±75.1μm to 280.1±41.8μm. The BCVA in the 1+PRN group increased from 0.79±0.20 to 0.42±0.14 and the CMT decreased from 472.7±80.7μm to 271.6±39.6μm. There was no statistically significant difference in BCVA or CMT between two groups at any time point(<i>P</i>>0.05). During the study period, the mean number of injections were 3.64±0.66 and 2.78±0.94 in 1+PRN group and 3+PRN group respectively(<i>P</i>>0.05). In both groups, age, duration, baseline BCVA and integrity of photoreceptor inner and outer segment(IS/OS)were associated with better VA at the 6mo after the first injection.<p>CONCLUSION: In IVC treatment for ME secondary to BRVO, 1+PRN and 3+PRN dosing regimens are both effective and achieved similar functional outcomes.
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Objective@#To investigate the effectiveness and safety of clinical pharmacists-directed vancomycin dosing and therapeutic drug monitoring (TDM), and to promote the individualized medication of vancomycin.@*Methods@#Information of hospitalized patients treated by vancomycin admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to October 2017 was collected retrospectively during study period, the patients were divided into pharmacists intervention and non-pharmacists intervention groups according to pharmacist-directed vancomycin dosing guideline or not. The individualized dosing regimen of vancomycin for the patients in pharmacists intervention group was guided by clinical pharmacists, this guideline was that pharmacists offered the TDM guidance, made the individualized dosage regimen of vancomycin, etc., which based on the patients' pathophysiology, condition, and the adjustments of increased dose or 24-hour continuous infusion vancomycin were made for patients if the steady-state trough concentrations fell below the target level. Vancomycin dosage was made for patients in the non-pharmacists intervention group by physicians only based on vancomycin instructions or clinical experience. The vancomycin dosing, TDM, microorganism culture, renal function, 30-day mortality rate, and length of hospital stay were recorded. The appropriateness of TDM for vancomycin was defined as a blood collection within 1 hour of the next scheduled dose after steady state achieved. The rationality of the initial dosing regimen was determined based on the vancomycin application guidelines issued by Infectious Diseases Society of America (IDSA) in 2009.@*Results@#A total of 258 patients were enrolled, and there were 158 patients in the non-pharmacists intervention group and 100 in pharmacists intervention group. The appropriateness of TDM for vancomycin in pharmacists intervention group was significantly improved as compared with that in non-pharmacists intervention group [87.0% (87/100) vs. 69.6% (110/158), P < 0.01], the percentage of first trough serum concentrations drawn on day 3 after steady state achieved was significantly increased [51.0% (51/100) vs. 37.3% (53/142), P < 0.05]. Compared with the non-pharmacists intervention group, the percentages of patients who received appropriate initial dosing and attained the initial target therapeutic range in pharmacists intervention group were significantly increased [87.4% (76/87) vs. 68.2% (75/110), 51.7% (45/87) vs. 30.9% (34/110), both P < 0.01], the percentage of patients whose vancomycin dosing regimen was adjusted based on TDM results was also significantly increased [54.0% (47/87) vs. 15.5% (17/110), P < 0.01], the rate of vancomycin serum concentrations reaching the standard was increased [70.1% (61/87) vs. 32.7% (36/110), P < 0.01], and a lower number of patients in sub- or supra-therapeutic range was observed in pharmacists intervention group [27.6% (24/87) vs. 46.4% (51/110), 2.3% (2/87) vs. 20.9% (23/110), both P < 0.01]. In addition, a lower incidence of vancomycin-induced acute kidney injury (AKI) was observed in pharmacists intervention group as compared with that in non-pharmacists intervention group [0 (0/87) vs. 6.4% (7/110), P < 0.01]. No significant difference was observed in the microorganism culture, 30-day mortality rate or length of hospital stay between the two groups. Among the 87 patients in pharmacists intervention group, the vancomycin dosing was adjusted for 42 patients who did not attain the target therapeutic range, increasing the dose of vancomycin was made for 22 patients, 24-hour continuous infusion was made for 20 patients. Compared with the only increasing vancomycin dose group, vancomycin continuous infusion for 24 hours could significantly increase the serum trough concentration (mg/L: 18.0±6.7 vs. 12.5±5.8, P < 0.05), and reduce daily dosage (mg/kg: 27.1±7.1 vs. 36.6±9.2, P < 0.01).@*Conclusions@#The implementation of a pharmacist-directed vancomycin dosing guideline based on TDM optimized vancomycin dosing regimen, improved the accuracy and timeliness of TDM for vancomycin, achieved a higher percentage of levels within the therapeutic range, and a lower incidence of vancomycin-induced AKI.
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OBJECTIVE: To introduce the research progress of dosage regimen of piperacillin/tazobactam and its rational offer reference for clinical use. METHODS: The domestic and oversea pertinent articles were searched, analyzed and summarized, and the difference between prolonged infusion or continuous infusion and traditional infusionin pharmacodynamics and clinical trials were compared. RESULTS: The optimized dosage regimen could achieve higher pharmacodynamics goals, with clinical efficacy and bacterial clearance not inferior to the traditional dosage regimen. CONCLUSION: The prolonged or continuous infusion strategy should be recommended for piperacillin/tazobactam in the clinic.
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OBJECTIVE: To establish a population pharmacokinetic model of intravenous infusing busulfan in HSCT patients, and to explore physiological and pathological factors which may influence the pharmacokinetic parameters. METHODS: We have collected clinical history information of 35 patients undergoing HSCT surgery and taking busulfan intravenous infusion for treatment. These information such as physiological and pathological factors and busulfan concentration data were used to perform the population pharmacokinetic analysis by applying the method of nonlinear mixed effects modeling(NONMEM). RESULTS: A statistical model of busulfan is established, including variables such as body weight, sex, serum creatinine clearance. The success of 973 out of 1 000 times resampling trials (by bootstrap) shows that the newly parameters value are very close to the estimate value calculated from the final model by NONMEM, which demonstrates the established population pharmacokinetic model of busulfanis stable, effective and predictable. CONCLUSION: The population pharmacokinetic model is established, which is capable of depicting the pharmacokinetic characteristics of busulfan. It is found that patients' weight, gender and creatinine clearance influence pharmacokinetic parameters, which can be useful and valuable for the clinical individualized dosing regimens.
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Objective To offer reference to reasonable clinical use of piperacillin sodium sodium-tazobactam sodium .Methods We reviewed pharmacokinetic/pharmacodynamic studies , clinical trails and implementation of piperacillin sodium-tazobactam sodi-um alternative dosing regimen in recent .Results The alternative dosing regimens , prolonged and continuous infusion , could maximise the likelihood of achieving desirable pharmacodynamic targets and improve clinical effectiveness .Conclusion It’ s needed to improve the strategies of alternative dosing regimens for clinical practice .
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BACKGROUND: Teicoplanin is a glycopeptide antibiotic that is widely used in clinical practice for the treatment of infections caused by drug-resistant Gram-positive bacteria. The aim of this study was to analyze plasma teicoplanin concentrations to determine the percentage of patients in whom therapeutic concentrations of teicoplanin were achieved in clinical practice. MATERIALS AND METHODS: The plasma teicoplanin concentrations of hospitalized patients receiving treatment at a teaching hospital were retrospectively analyzed. The target level was defined as a plasma teicoplanin concentration of 10 mg/L or greater, since this was generally regarded as the lower limit of the optimal concentration range required for the effective treatment of a majority of infections. RESULTS: Patients with sub-optimal (< 10 mg/L) plasma teicoplanin concentrations constituted nearly half of the total study population. The majority of these patients received the recommended loading dose, which were three 400 mg doses administered every 12 hours. Sub-group analysis showed a trend that the group receiving loading dose was more likely to reach the optimal teicoplanin concentration. CONCLUSIONS: The data revealed that a significant proportion of patients in clinical practice achieved only sub-optimal teicoplanin concentrations, which emphasizes the importance of the mandatory use of loading dose and routine therapeutic drug monitoring. Treatment reassessment and simulation of individual dose regimens may also be necessary to achieve optimal drug concentrations.
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Humans , Drug Monitoring , Gram-Positive Bacteria , Hospitals, Teaching , Plasma , Retrospective Studies , TeicoplaninABSTRACT
This article describes the definition of the term TDM (i. e. therapeutic drug monitoring), presents the past history, present status and future prospects of individualized dosing regimen, and emphasizes the role of population pharmacokinetics and one point feedback Bayesian method played in the design of dosing regimen.