Favipiravir pharmacokinetics in COVID-19 patients with moderate to severe kidney dysfunction: Lessons learned for future use.

OBJECTIVE: There is limited information on favipiravir pharmacokinetics in critically ill patients and no studies on pharmacokinetics in patients with moderate and severe kidney dysfunction. The aim was to determine favipiravir pharmacokinetics (oral, 1,600 mg, q12h on day 1, then 600 mg, q12h for 4 days) in critically ill COVID-19 patients with kidney dysfunction and to compare those with observations reported in healthy adults. MATERIALS AND METHODS: In a descriptive study, blood samples taken from patients meeting the relevant criteria (estimated glomerular filtration rate < 60 mL/min) were collected and analyzed. Analysis of blood samples was done by high performance liquid chromatography (HPLC), and the maximal concentration (Cmax), the time of maximal concentration (tmax), half-life (T1/2) and area under the curve (AUC0-12h) of favipiravir were calculated (WinNonlin) and compared to reported data in healthy subjects after first administration. RESULTS: Based on analysis of samples collected in 7 patients, the Cmax (29.99 vs. 64.5 µg/mL) of favipiravir was decreased, T1/2 (5.8 vs. 4.8 hours) longer, tmax delayed, while total exposure was lower (AUC0-12: 192.53 vs. 446.09 µg/mL) compared to reported data in healthy subjects after first administration. Exposure remained lower up to day 5. CONCLUSION: In patients with kidney dysfunction related to COVID-19, favipiravir did not reach the expected exposure. This may be due to poorer and delayed absorption, and subsequent altered disposition. Population pharmacokinetic and mechanistic studies are needed to better explore the relevant covariates and to determine the optimal dose in these patients, as this drug is likely of relevance for other indications.

Evaluation of regular insulin adsorption to polypropylene bag and polyvinyl chloride infusion set.

AIM: Clinical application of insulin infusion therapy is usually accomplished with regular human insulin. It is known that the regular insulin adsorbed to the hydrophobic surfaces and different approaches were implemented into the clinical practices. It was aimed to evaluate the rate of adsorption of insulin to polypropylene (PP) bags and polyvinyl chloride (PVC) infusion sets and stability of insulin during the infusion. METHODS: A 100 IU insulin was added to PP bags containing 100 mL of 0.9% NaCl solution (n = 6). The infusion was started at a rate of 2 mL/h using infusion sets in the PVC structure. Insulin quantification was performed in the samples taken both from the bag and from the end tip of the infusion set during infusion. The stability of insulin solutions stored at room (+25°C) and refrigerator (+4°C) temperatures were compared. Samples were analysed using reverse-phase high-performance liquid chromatography. RESULTS: No statistically significant difference was found between the concentrations of the samples taken from the bags stored at room and refrigerator temperatures at the 4th, 12th, and 24th hours (P > .05). It was seen that the adsorption rate of insulin to PVC set was 57% and PP bags is at most 5% at the 24th hour. CONCLUSION: When PP bags are used for insulin infusion, it is predicted that 24-hour change can be made instead of frequent change. In addition, losses caused by the high rate of insulin adsorption to PVC infusion sets should be considered and PP infusion sets would be the better option to use if available.

Evaluation of lipid profiles in patients treated with capecitabine

Background/aim: Capecitabine is a prodrug of 5-fluorouracil and has shown significant antitumor activity. The main adverse effects are hand-foot syndrome, diarrhea, and dermatitis. In recent years, hypertriglyceridemia has been reported in patients treated with capecitabine. Dyslipidemia is a rare but important side effect of capecitabine. The aim of this study is to examine the changes in lipid levels during capecitabine treatment and to raise awareness of pharmacovigilance. Materials and methods: In this retrospective study, it was aimed to analyze lipid metabolism after capecitabine treatment and is intended to contribute to the formation of a pharmacoepidemiological database. For this purpose, triglyceride, cholesterol, HDL, LDL, ALT, AST, ALP, MCV, and Hb blood levels of 57 patients treated with capecitabine at the Department of Medical Oncology, Faculty of Medicine, Çukurova University, were examined before and after five cycles of treatment. Results: Blood triglyceride and cholesterol levels were significantly increased after capecitabine treatment. The increase in triglyceride levels was higher than the increase in cholesterol levels. Conclusion: In the light of these findings, monitoring of the lipid profile should be considered in cancer patients treated with capecitabine.

Population pharmacokinetics in critically ill neonates and infants undergoing extracorporeal membrane oxygenation: a literature review.

Extracorporeal membrane oxygenation (ECMO) increases circulating blood volume, causes capillary leak and temporarily alters kidney function. Consequently, pharmacokinetics (PK) can be affected. When applied to neonates and infants, additional dose adjustments are a major concern, as the volume of distribution (Vd) is already generally greater for water-soluble drugs and the clearance (Cl) of drugs eliminated by glomerular filtration is reduced. A systematic search was performed on MEDLINE (1994-2022) using a combination of the following search terms: "pharmacokinetics", "extracorporeal membrane oxygenation" and "infant, newborn" using Medical Subject Headings search strategy. Nine out of 18 studies on 11 different drugs (vancomycin, meropenem, fluconazole, gentamicin, midazolam, phenobarbital, theophylline, clonidine, morphine, cefotaxime and cefepime) recommended dose increase/decrease by determining PK parameters. In other studies, it has been suggested to adjust the dose intervals. While the elimination half-life (t1/2) and Vd mostly increased for all drugs, the Cl of the drugs has been shown to have variability except for midazolam and morphine. There are a limited number of population PK studies in neonates and infants undergoing ECMO circuits. Despite some divergences, the general pattern suggests an increase in Vd and t1/2, an increased, stable or decreased Cl, and an increase in variability. Consequently, and if possible, therapeutic drug monitoring and target concentration intervention are strongly recommended to determine appropriate exposure and doses for neonates and infants undergoing ECMO support.

Evaluation of the effect of antibiotics used during parenteral nutrition treatment on Candidemia.

OBJECTIVE: Parenteral nutrition is an important risk factor for candidemia. In this risk analysis study, the effect of previous antibiotic administration apart from the length of hospital stay, duration of Parenteral nutrition treatment, and Candida score parameters on developing candidemia was evaluated in the non-neutropenic patients receiving Parenteral nutrition treatment. METHODS: In this double center, retrospective, and cross-sectional study, the data of patients who received Parenteral nutrition treatment were collected. Patients with or without candidemia after the initiation of Parenteral nutrition treatment were compared in terms of demographic features, Candida score, length of hospital stay, duration of Parenteral nutrition treatment, and previous use of antibiotics. Then, predictor factors affecting the probability of candidemia during Candida growth time were determined by the Cox regression analysis. RESULTS: A total of 148 patients (59.5% males) were included and 16 (10.81%) of these had candidemia after initiation of parenteral nutrition treatment. The median (min-max) duration of parenteral nutrition treatment was 11 (4-72) days and the Candida growth time was 13 (7-29) days. Statistically significant differences were found between patients with or without candidemia groups in terms of length of hospital stay (p<0.001), duration of parenteral nutrition treatment (p<0.001), and Candida score (p<0.001). To determine the effect of these variables and antibiotics on candidemia, length of hospital stay [Hazard Ratio 1.030; p=0.021] and piperacillin-tazobactam (Hazard Ratio 5.626; p=0.030) were found significant and independent risk factors on the development of candidemia. CONCLUSION: There are some well-known risk factors including length of hospital stay, duration of Parenteral nutrition treatment, and Candida score; the potential impact of piperacillin-tazobactam administration should also be considered since they may be effective on the development of candidemia.

Physicians' knowledge of potential covid-19 drug-drug interactions: An online survey in turkey.

OBJECTIVES: Given the many medications used to treat novel coronavirus disease (COVID-19) and its comorbidities and complications, the risk of drug-drug interactions (DDIs) and resulting patient harm is concerning. This study aimed to shed light on physicians' knowledge of potential DDIs related to COVID-19 treatment, to determine the effect of an information brief about these DDIs on their correct response rates, and to identify factors associated with higher levels of knowledge about these DDIs. METHODS: The knowledge of physicians regarding the clinical significance and intervention of 7 common potential DDIs during COVID-19 treatment was evaluated via an online survey. Using a pretest-posttest design, the physicians completed a multiple-choice questionnaire first using their existing knowledge, then received an information brief about the DDIs and completed the same questionnaire again. Pretest and posttest scores were evaluated and factors affecting correct response rates were determined using correlation, regression, and post-hoc analyzes. RESULTS: A total of 244 physicians participated in the survey, 147 (60.2%) of whom were involved in the treatment of COVID-19 patients. After the information brief, there were significant increases in the number of correct responses for both clinical significance and interventions (p < 0.0001). In comparisons of pretest knowledge, physicians involved in the treatment of COVID-19 patients showed significantly higher correct response rate for interventions compared to physicians who had not treated COVID-19 patients (p = 0.003). Post-hoc analysis to compare pretest correct intervention responses among all medical specialties revealed significant differences between infectious diseases and family practice (mean difference: 1.059; p = 0.005) and between internal medicine and family practice (mean difference: 1.771; p < 0.0001). CONCLUSION: Physicians involved in the treatment of COVID-19 patients had more knowledge regarding clinical significance and appropriate management of potential DDIs than those not involved. Therefore, it may be beneficial to organize trainings and issue guidelines about potential DDIs for physicians during the COVID-19 pandemic.

Evaluation of the effect of antibiotics used during parenteral nutrition treatment on Candidemia

SUMMARY OBJECTIVE: Parenteral nutrition is an important risk factor for candidemia. In this risk analysis study, the effect of previous antibiotic administration apart from the length of hospital stay, duration of Parenteral nutrition treatment, and Candida score parameters on developing candidemia was evaluated in the non-neutropenic patients receiving Parenteral nutrition treatment. METHODS: In this double center, retrospective, and cross-sectional study, the data of patients who received Parenteral nutrition treatment were collected. Patients with or without candidemia after the initiation of Parenteral nutrition treatment were compared in terms of demographic features, Candida score, length of hospital stay, duration of Parenteral nutrition treatment, and previous use of antibiotics. Then, predictor factors affecting the probability of candidemia during Candida growth time were determined by the Cox regression analysis. RESULTS: A total of 148 patients (59.5% males) were included and 16 (10.81%) of these had candidemia after initiation of parenteral nutrition treatment. The median (min-max) duration of parenteral nutrition treatment was 11 (4-72) days and the Candida growth time was 13 (7-29) days. Statistically significant differences were found between patients with or without candidemia groups in terms of length of hospital stay (p<0.001), duration of parenteral nutrition treatment (p<0.001), and Candida score (p<0.001). To determine the effect of these variables and antibiotics on candidemia, length of hospital stay [Hazard Ratio 1.030; p=0.021] and piperacillin-tazobactam (Hazard Ratio 5.626; p=0.030) were found significant and independent risk factors on the development of candidemia. CONCLUSION: There are some well-known risk factors including length of hospital stay, duration of Parenteral nutrition treatment, and Candida score; the potential impact of piperacillin-tazobactam administration should also be considered since they may be effective on the development of candidemia.