This study aimed to explore pharmacokinetics of voriconazole and its covariates in lung transplant recipients using population approach in order to propose dosing individualization. Data from routine therapeutic drug monitoring in adult lung transplant recipients treated with oral voriconazole were analysed with a three-stage population pharmacokinetic model using nonlinear mixed-effects modelling. Monte Carlo simulations based on final voriconazole pharmacokinetic model were used to generate the theoretical distribution of pharmacokinetic profiles at various dosing regimens. A total of 78 voriconazole serum concentrations collected from 40 patients were included in pharmacokinetic analysis. The only significant covariate was age for voriconazole clearance. Population voriconazole apparent clearance started at 32.26 L/h and decreased by 0.021 L/h with each year of patient's age, while population apparent volume of distribution was 964.46 L. Based on this model, we have proposed an easy-to-use dosing regimen consisting of a loading dose of 400 mg every 12 h for the first 48 h of treatment followed by maintenance dose of 300 mg every 12 h in patients aged up to 59 years, or by maintenance dose of 200 mg every 12 h in patients aged above 59 years.
- MeSH
- biologické modely MeSH
- dospělí MeSH
- lidé MeSH
- metoda Monte Carlo MeSH
- monitorování léčiv * MeSH
- plíce MeSH
- příjemce transplantátu * MeSH
- senioři MeSH
- vorikonazol farmakokinetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
Obezita, ale i malnutrice u starší populace vzbuzuje stále větší obavy. Podávání léčiv obézním pacientům je obtížné, protože doporučené dávky jsou založeny na farmakokinetických údajích získaných od jedinců s hmotností ve zdravém rozmezí v produktivním věku. Proto může dojít při stanovení vhodné dávky u obézní seniorské populace dojít k chybám. Vlivem stárnutí, ale i obezitou nebo malnutricí samotnou mohou být ovlivněny všechny fáze farmakokinetiky léčiv (absorpce, distribuce, metabolismus a eliminace). Tyto změny se často v případě kombinace obezity a vyššího věku potencují. Problémem také je, že ne všechna léčiva jsou ovlivněna stejně, proto je třeba znát vliv věku a obezity na kinetiku konkrétní posuzované látky. Bolestí trpí 50 % seniorů v domácím prostředí a až 80 % během hospitalizace. Kromě obecných poznatků o vlivu věku, ale i obezity a malnutrice na kinetiku léčiv uvádí tento přehled farmakokinetické změny analgetik způsobené jak obezitou, tak i malnutricí.
Both obesity and malnutrition in the elderly population are raising concerns. As majority of pharmacokinetic data are obtained from subjects with a healthy weight range in productive age, administration of correct dosing of drugs to obese elderly patients is quite challenging. All phases of the pharmacokinetics of drugs (absorption, distribution, metabolism and elimination) are potentially affected by the effect of aging but also by obesity or malnutrition. These changes are often potentiated in the case of a combination of obesity and older age. The problem is also that not all drugs are affected in the same way, therefore it is necessary to know the influence of age and obesity on the kinetics of the particular substance being assessed. 50% of seniors suffer from pain at home and up to 80% during hospitalization. In addition to general knowledge about the effect of age but also obesity and malnutrition on the kinetics of drugs, this overview presents the pharmacokinetic changes of analgesics caused by both obesity and malnutrition.
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). METHODS: A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. RESULTS: Patients with estimated GFR (eGFR) <30 mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30 mL/min (89.75 vs 186.0 mg/L, P < .0001; 200.5 vs 830.0 mg/L, P < .0001; and 126.0 vs 408.0 mg/L, P < .0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10-13 h after dose administration was dependent on eGFR (r2 = 0.6144, P < .0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100 mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. CONCLUSION: Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity.
- Publikační typ
- časopisecké články MeSH
PURPOSE OF REVIEW: Oral drug absorption after bariatric surgery is likely to be altered, but the impact of different bariatric surgery procedures on individual drugs is not uniform. The aim of this article is to describe factors influencing the bioavailability of orally administered drugs after bariatric surgery and to provide readers with practical recommendations for drug dosing. We also discuss the medications that may be harmful after bariatric surgery. RECENT FINDINGS: The fundamental factors for enteral drug absorption are the production of gastric acid; the preserved length of the intestine, i.e., the size of the absorption surface and/or the preserved enterohepatic circulation; and the length of common loop where food and drugs are mixed with digestive enzymes and bile acids. Bypassing of metabolizing enzymes or efflux pumps and changes in intestinal motility can also play an important role. Significant changes of drug absorption early after the anatomic alteration may also be gradually ameliorated due to gradual intestinal adaptation. The most affected drugs are those with low or variable bioavailability and those undergoing enterohepatic circulation. Attention should also be paid to oral drug formulations, especially in the early postoperative period, when immediate-release and liquid formulations are preferred. The changes in oral bioavailability are especially clinically meaningful in patients treated with drugs possessing narrow therapeutic index (e.g., oral anticoagulants, levothyroxine, and anticonvulsants) or in acute conditions (e.g., anti-infectives); nevertheless, it may also influence the therapeutic value of chronic therapy (e.g., antidepressants. antihypertensives, antiplatelets, statins, PPIs, contraceptives, and analgesics); therapeutic effect of chronic therapy is further influenced by pharmacokinetic alterations resulting from weight loss. Therapeutic drug monitoring, periodical clinical evaluation, and adequate dose adjustments are necessary. Due to safety reasons, patients should avoid oral bisphosphonates, regular use of non-steroidal anti-inflammatory drugs, and, if possible, corticosteroids after bariatric surgery.
- MeSH
- bariatrická chirurgie * metody MeSH
- biologická dostupnost MeSH
- gastrektomie MeSH
- hmotnostní úbytek MeSH
- lidé MeSH
- morbidní obezita * chirurgie MeSH
- žaludeční bypass * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: There are no clear guidelines on how to handle immunosuppression in lung transplant recipients (LTRs) infected by SARS-CoV-2. Antimetabolite reduction with corticosteroid escalation is the most frequent strategy. The aim of this study was to determine the effect of this therapeutic approach on the incidence of de novo donor specific-antibodies (dnDSA). METHODS: We retrospectively analysed a cohort of 27 LTRs diagnosed with SARS-CoV-2 infection between September 2020 and April 2021 with available anti-HLA antibodies screening before and after infection. Managed as per the centre's SARS-CoV-2 protocol, the treatment modalities included specific virostatic treatment, convalescent plasma administration, reduction or discontinuation of mycophenolate and transient corticosteroid escalation initiated in the second week post-infection. RESULTS: All 27 patients received virostatics: 15 (55.6%) remdesivir and 12 (44.4%) favipiravir. In addition, 18 patients (66.7%) underwent convalescent plasma therapy. Of the 27 patients, 25 (92.6%) received mycophenolate as a part of their maintenance immunosuppressive regimen, which was temporarily reduced in 10 (37%) and discontinued in 15 LTRs (55.6%), the median resumption times for mycophenolate daily doses of at least 1000 mg being 13 days (IQR 11.0-63.5) and 59 days (IQR 26.0-130.0), respectively. Corticosteroids were escalated in 25 patients (92.6%), of whom 9 (33.3%) received IV methylprednisolone (median 80 mg/day; IQR 80-187.5) and 16 (59.3%) had oral prednisone adjusted (median 20 mg/day; IQR 16.3-38.8). The median time to revert to the corticosteroid dosage of ≤20 mg/day was 42 days (IQR 36.0-87.0). Notably, no dnDSA were detected in any LTR between 1 and 9 months from the onset of the SARS-CoV-2 infection. CONCLUSION: Our findings suggest that antimetabolite cessation with a transient corticosteroid escalation is a safe therapeutic strategy regarding anti-HLA dynamics in SARS-CoV-2 infected LTRs.
- MeSH
- antilymfocytární sérum MeSH
- antimetabolity MeSH
- COVID-19 * epidemiologie MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- incidence MeSH
- lidé MeSH
- plíce MeSH
- příjemce transplantátu MeSH
- protilátky MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- sérologická léčba covidu-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose.
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Ciprofloxacin induces rare neuro-psychiatric adverse drug reactions (ADRs) that are, as yet, not possible to predict due to unknown predisposition factors. BACKGROUND: The aim of the analysis was to assess the frequency of neuro-psychiatric ADRs and to identify potential risk factors that predisposed patients to ciprofloxacin neurotoxicity. METHODS: This observational retrospective study involved the evaluation of the medical records of patients in the Nephrology department and 3rd Internal Clinic of the General University Hospital in Prague. RESULTS: The overall incidence of neurological ADRs was 3.6 %. No neurological ADRs developed in patients aged less than 70 years. The covariates that were significantly more prevalent in the patients who developed neuropsychiatric ADRs were as follows: higher age, a history of neuropsychiatric disorders and the use of anticonvulsants. The administration of drugs from other ATC groups, gender, weight, body mass index, body surface area, renal functions, level of C-reactive protein at the beginning of treatment and the total daily dose/kg did not differ significantly between the two groups. CONCLUSION: Ciprofloxacin neuropsychiatric ADRs are more frequent in older patients with a history of neurologic or psychiatric disorders. No other tested covariates were proven to predispose patients to neuropsychiatric ADRs during treatment with ciprofloxacin (Tab. 2, Ref. 20).
Mucormycosis is a rare invasive fungal disease diagnosed in immunocompromised patients, including those with diabetes or iron overload, and in patients treated for hematological malignancies or after transplantation. Isavuconazole is a triazole antifungal effective against Mucorales with good tolerability, but with potential for relatively high interindividual variability in pharmacokinetics. This report demonstrates the case of a lung transplant recipient treated with isavuconasole that exhibits a very long elimination half-life of 159 hours, and discusses the practical implications of this finding for dosage adjustment and need for therapeutic drug monitoring.
A narrative review of the literature was conducted to determine if the administration of methylene blue (MB) in humans has potential risks. Studies were identified from MEDLINE, Web of Science, Scopus, and Cochrane. MB is a diagnostic substance used during some diagnostic procedures and also a part of the treatment of several diseases including methemoglobinemia, vasoplegic syndrome, fosfamide-induced encephalopathy, and cyanide intoxication, and the detection of leaks or position of parathyroid corpuscles during surgery. Although the use of MB is historically justified, and it ought to be safe, because it originated as a diagnostic material, the basic toxicological characteristics of this substance are unknown. Despite reports of severe adverse effects of MB, which could significantly exceed any possible benefits evaluated for the given indication. Therefore, the clinical use of MB currently represents a controversial problem given the heterogeneity of available data and the lack of preclinical data. This is in conflict with standards of safe use of such substances in human medicinal practice. The toxic effects of the application of MB are dose-dependent and include serious symptoms such as hemolysis, methemoglobinemia, nausea and vomitus, chest pain, dyspnoea, and hypertension. Some countries regard MB as harmful because of the resulting skin irritation and triggering of an adverse inflammatory response. MB induced serotoninergic toxicity clinically manifests as neuromuscular hyperactivity. This review aims to summarize the current understanding concerning the indications for MB administration and define the potential adverse effects of MB.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
