ResearchPad - pharmacokinetics-and-disposition Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study]]> To assess whether extracorporeal treatment (ECTR) improves outcome of patients with metformin-associated lactic acidosis (MALA) and to evaluate the clinical applicability of the Extracorporeal Treatments in Poisoning Workgroup (EXTRIP) criteria for starting ECTR in metformin poisoning.MethodsPatients with metformin serum concentrations above 2 mg/l who were admitted in the Deventer Teaching Hospital between January 2000 and July 2019 and complied with the definition of MALA (pH < 7.35 and lactate concentration > 5 mmol/l) were included. Mortality and clinical parameters of patients treated with ECTR or not were compared. In addition, treatment of MALA in clinical practice was verified against the criteria of EXTRIP.ResultsForty-two patients were included. Lactate (13.8 versus 10.5 mmol/l, p = 0.01), creatinine (575 versus 254 umol/l, p < 0.01)), metformin (29.4 versus 8.6 mg/l, p < 0.01) concentrations, and vasopressor requirement (72% versus 23%, p < 0.01) were significantly higher in the ECTR-group. Blood pH (7.05 versus 7.19, p = 0.03) and bicarbonate (6 versus 11 mmol/l, p < 0.01) were significantly lower. Mortality, length of hospital stay, and mechanical ventilation requirement were not statistically different. In 83% of patients, treatment of MALA was in accordance with the EXTRIP criteria.ConclusionsAlthough there was no statistical benefit in mortality shown from ECTR, ECTR might be lifesaving in MALA, considering the ECTR-group was significantly sicker than the non-ECTR-group.The majority of patients were treated in line with the EXTRIP criteria. Severity of lactic acidosis and renal impairment were the main indications for initiating ECTR.Electronic supplementary materialThe online version of this article (10.1007/s00228-020-02857-5) contains supplementary material, which is available to authorized users. ]]> <![CDATA[Evaluation of limited sampling strategies for tacrolimus]]>


In literature, a great diversity of limited sampling strategies (LSS) have been recommended for tacrolimus monitoring, however proper validation of these strategies to accurately predict the area under the time concentration curve (AUC0–12) is limited. The aim of this study was to determine whether these LSS might be useful for AUC prediction of other patient populations.


The LSS from literature studied were based on regression equations or on Bayesian fitting using MWPHARM 3.50 (Mediware, Groningen, the Netherlands). The performance was evaluated on 24 of these LSS in our population of 37 renal transplant patients with known AUCs. The results were also compared with the predictability of the regression equation based on the trough concentrations C0 and C12 of these 37 patients. Criterion was an absolute prediction error (APE) that differed less than 15% from the complete AUC0–12 calculated by the trapezoidal rule.


Thirteen of the 18 (72%) LSS based on regression analysis were capable of predicting at least 90% of the 37 individual AUC0–12 within an APE of 15%. Additionally, all but three LSS examined gave a better prediction of the complete AUC0–12 in comparison with the trough concentrations C0 or C12 (mean 62%). All six LSS based on Bayesian fitting predicted <90% of the 37 complete AUC0–12 correctly (mean 67%).


The present study indicated that implementation of LSS based on regression analysis could produce satisfactory predictions although careful evaluation is necessary.