Plasma concentrations of remdesivir metabolite in a critical COVID-19 patient needing continuous venovenous haemodialysis.
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ABSTRACT:
SUBMITTER: Tempestilli M
PROVIDER: S-EPMC8116063 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSupplementation of calcium during continuous venovenous hemofiltration (CVVH) with citrate anticoagulation is usually titrated using a target blood ionized calcium concentration. Plasma calcium concentrations may be normal despite substantial calcium loss, by mobilization of calcium from the skeleton. Aim of our study is to develop an equation to calculate CVVH calcium and to retrospectively calculate CVVH calcium balance in a cohort of ICU-patients.MethodsThis is a single-center retrospective observational cohort study. In a subcohort of patients, all calcium excretion measurements in patients treated with citrate CVVH were randomly divided into a development set (n = 324 in 42 patients) and a validation set (n = 441 in 42 different patients). Using mixed linear models, we developed an equation to calculate calcium excretion from routinely available parameters. We retrospectively calculated calcium balance in 788 patients treated with citrate CVVH between 2014 and 2021.ResultsCalcium excretion (mmol/24 h) was - 1.2877 + 0.646*[Ca]blood,total * ultrafiltrate (l/24 h) + 0.107*blood flow (ml/h). The mean error of the estimation was - 1.0 ± 6.7 mmol/24 h, the mean absolute error was 4.8 ± 4.8 mmol/24 h. Calculated calcium excretion was 105.8 ± 19.3 mmol/24 h. Mean daily CVVH calcium balance was - 12.0 ± 20.0 mmol/24 h. Mean cumulative calcium balance ranged from - 3687 to 448 mmol.ConclusionDuring citrate CVVH, calcium balance was negative in most patients, despite supplementation of calcium based on plasma ionized calcium levels. This may contribute to demineralization of the skeleton. We propose that calcium supplementation should be based on both plasma ionized calcium and a simple calculation of calcium excretion by CVVH.
| S-EPMC10227114 | biostudies-literature
Project description:This study presents outcome and pharmacokinetics of arsenic trioxide (ATO) metabolites in patients on continuous venovenous haemodialysis (CVVHD). Of 3 acute promyelocytic leukaemia patients receiving CVVHD in management of acute kidney injury, only 1 patient was included. The patient presented disseminated intravascular coagulation and acute kidney injury before induction therapy was conducted. CVVHD was performed and ATO was initiated. Species of ATO metabolites in plasma and effluent were analysed using high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry. Plasma concentrations of AsIII , monomethylarsonic acid and dimethylarsinic acid with CVVHD were lower than those without CVVHD. Area under the concentration-time curve from 0 to the last sample with quantifiable concentration of AsIII without CVVHD was significantly higher than that with CVVHD (292.10 ng h/mL vs 195.86 ng h/mL, P = .037), which were not observed for monomethylarsonic acid and dimethylarsinic acid. Dialysate saturation of arsenic species was remarkable, especially for AsIII . Complete remission was achieved and renal function recovered. In this study, ATO can be used safely and effectively to treat acute promyelocytic leukaemia patients undergoing CVVHD without dose adjustment.
| S-EPMC6422666 | biostudies-literature
Project description:Extended-infusion ceftolozane-tazobactam treatment at 1.5 g every 8 h was used to treat multidrug-resistant Pseudomonas aeruginosa in a critically ill patient on continuous venovenous hemofiltration. Serum drug concentrations were measured at 1, 4, 5, 6, and 8 h after the start of infusion. Prefilter levels of ceftolozane produced a maximum concentration of drug (Cmax) of 38.57 ?g/ml, concentration at the end of the dosing interval (Cmin) of 31.63 ?g/ml, time to Cmax (Tmax) of 4 h, area under the concentration-time curve from 0 to 8 h (AUC0-8) of 284.38 ?g · h/ml, and a half-life (t1/2) of 30.7 h. The concentrations were eight times the susceptibility breakpoint for the entire dosing interval.
| S-EPMC4775955 | biostudies-other
Project description: Not available
| S-EPMC5152589 | biostudies-literature
Project description:AimsCitalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT.MethodsOur genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects.ResultsGenome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10(-9) ) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10(-16) ), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation.ConclusionsIn vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors.
| S-EPMC4137829 | biostudies-literature
Project description:BACKGROUND:The relationship between plasma concentration of sedatives and delirium is unknown. OBJECTIVE:We hypothesized that higher plasma concentrations of lorazepam are associated with increased delirium risk, whereas higher plasma concentrations of dexmedetomidine are associated with reduced delirium risk. METHODS:This prospective cohort study was embedded in a double-blind randomized clinical trial, where ventilated patients received infusions of lorazepam and dexmedetomidine. Plasma concentrations of these drugs and delirium assessments were measured at least daily. A multivariable logistic regression model accounting for repeated measures was used to analyze associations between same-day plasma concentrations of lorazepam and dexmedetomidine (exposures) and the likelihood of next-day delirium (outcome), adjusting for same-day mental status (delirium, coma, or normal) and same-day fentanyl doses. RESULTS:This critically ill cohort (n = 103) had a median age of 60 years (IQR: 48-66) with APACHE II score of 28 (interquartile range [IQR] = 24-32), where randomization resulted in assignment to lorazepam (n = 51) or dexmedetomidine (n = 52). After adjusting for same-day fentanyl dose and mental status, higher plasma concentrations of lorazepam were associated with increased probability of next-day delirium (comparing 500 vs 0 ng/mL; odds ratio [OR] = 13.2; 95% CI = 1.4-120.1; P = 0.02). Plasma concentrations of dexmedetomidine were not associated with next-day delirium (comparing 1 vs 0 ng/mL; OR = 1.1; 95% CI = 0.9-1.3; P = 0.45). CONCLUSIONS:In critically ill patients, higher lorazepam plasma concentrations were associated with delirium, whereas dexmedetomidine plasma concentrations were not. This implies that the reduced delirium risk seen in patients sedated with dexmedetomidine may be a result of avoidance of benzodiazepines, rather than a dose-dependent protective effect of dexmedetomidine.
| S-EPMC5930024 | biostudies-literature
Project description: Not available
| S-EPMC8354840 | biostudies-literature
Project description:While colistin is considered a last resort for the treatment of multidrug-resistant Gram-negative bacterial infections, there has been an increase in its use due to the increasing prevalence of drug-resistant infections worldwide. The pharmacology of colistin is complex, and pharmacokinetic data are limited, especially in patients requiring renal replacement therapy. As a result, dosing for patients who require renal replacement remains a challenge. Here, we present pharmacokinetic data for colistin from two burn patients (37 and 68 years old) infected with colistin-susceptible isoclonal Acinetobacter baumannii and receiving continuous venovenous hemofiltration (CVVH). To our knowledge, we are the first to examine data from before and during CVVH (for one patient), allowing analysis of the effect of CVVH on colistin pharmacokinetics. Pharmacokinetic/pharmacodynamic analysis indicated that a dose increase from 1.5 to 2.2 mg/kg of body weight colistin base activity on CVVH was insufficient to satisfy the target parameter of an AUC24/MIC (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of ? 60 at an MIC of ? 1 ?g/ml in one patient with residual endogenous renal function. Plasma concentrations of colistin ranged from 0 to 15 ?g/ml, with free colistin levels ranging from 0.4 to 2.2 ?g/ml. While both patients resolved their clinical infections and survived to discharge, colistin-resistant colonizing isolates resulted from therapy in one patient. The variabilities observed in colistin concentrations and pharmacokinetic characteristics highlight the importance of pharmacokinetic monitoring of antibiotics in patients undergoing renal replacement therapy.
| S-EPMC4291386 | biostudies-literature
Project description:It is known that continuous venonenous hemofiltration (CVVH) does not affect the plasma level of neutrophil gelatinase-associated lipocalin (pNGAL) in acute kidney injury (AKI) patients. However, because of the unique pathophysiology underlying AKI caused by sepsis, the effect of CVVH on pNGAL in this clinical setting is less certain. The purpose of this study was to determine the effect of CVVH on pNGAL in sepsis-induced AKI patients.Between August 1, 2014, and December 31, 2014, 42 patients with sepsis-induced AKI underwent CVVH in the general intensive care unit of our institution and were consecutively enrolled in this study. Prefilter, postfilter, and ultrafiltrate pNGAL measurements were taken at the initiation of continuous renal replacement therapy (CRRT) and repeated after 2, 4, 8, and 12 h (T0, T2h, T4h, T8h, and T12h, respectively). The mass transfer, plasma clearance, and sieving coefficient were calculated based on the mass conservation principle.Following CVVH initiation, we found that pNGAL in the ultrafiltrate decreased significantly (P?=?0.013); however, levels at the inlet and outlet showed no significant change (P?>?0.05 for both). Furthermore, there was no change in the total mass removal rate, total mass adsorption rate, and plasma clearance over time (P?>?0.05 for all), and a significant decrease in the sieving coefficient (P?=?0.007) was seen.The results of this study show a limited effect of CVVH on pNGAL in sepsis-induced AKI patients. This suggests that pNGAL may be used as an indicator of renal progression in these patients. However, a larger study to confirm these findings is needed.ClinicalTrials.gov, NCT02536027 . Retrospectively registered on 20th August 2015.
| S-EPMC5072349 | biostudies-literature
Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F2? (PGF2?) in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF2? in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF2? in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF2?, a stable metabolite of PGF2?.MethodsWe measured plasma concentrations of 15-keto-dihydro PGF2? in 91 IPF patients and compared these values with those of controls (n?=?25). We further investigated the relationships of plasma 15-keto-dihydro PGF2? concentrations with disease severity and mortality.ResultsPlasma concentrations of 15-keto-dihydro PGF2? were significantly higher in IPF patients than controls (p<0.001). Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (Rs [correlation coefficient]?=?-0.34, p?=?0.004), forced vital capacity (Rs?=?-0.33, p?=?0.005), diffusing capacity for carbon monoxide (Rs?=?-0.36, p?=?0.003), the composite physiologic index (Rs?=?0.40, p?=?0.001), 6-minute walk distance (Rs?=?-0.24, p?=?0.04) and end-exercise oxygen saturation (Rs?=?-0.25, p?=?0.04) when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk?=?1.049, p?=?0.002) and plasma 15-keto-dihydro PGF2? concentrations (relative risk?=?1.005, p?=?0.002) were independently associated with an increased risk of mortality.ConclusionsWe demonstrated significant associations of plasma concentrations of PGF2? metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF2? in human IPF.
| S-EPMC3679025 | biostudies-literature