1,721,277 research outputs found
Pharmacology of drugs for hyperuricemia: Mechanisms, kinetics and interactions
No full textThe pharmacological profile of drugs for hyperuricemia is reviewed. These agents may reduce the amount of uric acid in blood by means of two different ways: (1) by reducing uric acid production through the inhibition of the enzyme xanthine oxidase (as allopurinol); (2) by increasing uric acid clearance through an inhibition of its renal tubular reabsorption (as probenecid), or through its metabolic conversion to a more soluble compound (as urate oxidase). Allopurinol is rapidly converted in the body to the active metabolite oxypurinol whose total body exposure may be 20-fold greater than that of the parent compound due to a much longer elimination half-life. Allopurinol undergoes several pharmacokinetic interactions with concomitant administered drugs, some of which may be potentially hazardous (especially with mercaptopurine and azathioprine). Probenecid is an uricosuric agent which undergoes extensive hepatic metabolism and whose elimination after high doses may become dose dependent. It may inhibit renal tubular secretion of several coadministered agents, including methotrexate and sulphonylureas. Rasburicase is a recombinant form of the enzyme urate oxidase which catalyzes the conversion of uric acid to the more soluble compound allantoin. Unlike allopurinol, it does not promote accumulation of hypoxanthine and xanthine in plasma, thus preventing the risk of xanthine nephropathy. Rasburicase showed no significant accumulation in children after administration of either 0.15 or 0.20 mg/kg/daily for 5 days. Rasburicase probably undergoes peptide hydrolysis and in in vitro studies was shown neither to inhibit or induce cytochrome P450 isoenzymes nor to interact with several drugs, so that no relevant interaction is expected during cotreatment in patients
Daptomycin in solid organ transplantation: Consideration of dosage adjustments in renal impairment
No full textTeicoplanin and therapeutic drug monitoring: An update for optimal use in different patient populations
No full textIndividualization of antimicrobial treatment based on real-time therapeutic drug monitoring (TDM) and dosing adaptation may represent an important tool in the antimicrobial stewardship programs. Teicoplanin is a glycopeptide hydrophilic antibiotic whose pharmacokinetic behavior may consistently vary among different patient populations. Nowadays it is generally recognized that the effective trough (Cmin) plasma level of tecoplanin should be of at least 10–15 mg/L for the treatment of mild infections, and of 15–30 mg/L for the treatment of deep-seated infections and/or of severe infections. The aim of this viewpoint is to provide an update for optimal use of teicoplanin TDM in different patient populations. Available literature supports TDM of Cmin as a helpful approach in addressing appropriate treatment with teicoplanin, with a frequency of assessment that should be guided by the severity of the infection and/or by the complexity of the pathophysiological status of the patient
From bench to bedside: Perspectives on the utility of pharmacokinetics/pharmacodynamics in predicting the efficacy of antifungals in invasive candidiasis
No full textThe aim of this perspective is to give an overlook on the utility of pharmacokinetics/pharmacodynamics (PK/PD) in predicting the efficacy of antifungals in invasive candidiasis. Overall, from the available literature it appears that bridging data of PK/PD of antifungals from the laboratory to the clinic for the treatment of invasive candidiasis are feasible only partially. Fluconazole is the only antifungal agent having the pharmacodynamic threshold of efficacy identified in experimental animal models convincingly validated in the clinical setting of invasive candidiasis as well. Conversely, for voriconazole and posaconazole data on this topic are very limited. For the echinocandins, robust PK/PD identified in the laboratory represented the rationale for defining differential clinical breakpoints of echinocandins against different species of Candida by the regulatory agencies. However, translation of the findings in the clinical setting provided conflicting results. Data on PK/PD of amphotericin B and flucytosine in models of invasive candidiasis are quite limited, and clinical studies assessing the role of drug exposure on efficacy are currently lacking. The expectation is that prospective studies could test more and more frequently the validity of experimental PK/PD data of antifungals in the clinical setting of invasive candidiasis. The findings could represent a step forward in addressing adequate antifungal stewardship programmes
Mutant Prevention Concentration: Is it significant in the clinical practice? | Mutant Prevention Concentration: È un parametro significativo nella pratica clinica?
No full textWhat is the Role of Fluoroquinolones in Intensive Care?
No full textFluoroquinolones are a class of antibiotics that are widely used in the treatment of a number of severe infections frequently observed in intensive care units (ICU). From a pharmacodynamic point of view, the optimal conditions for guaranteeing clinical recovery and preventing the occurrence of resistance to this class of antibiotics are represented by the ratios of C max/MIC >12.2 and AUC24h/MlC equal to 100-125 hours for Gram-negative bacteria, and about 30-40 hours for Gram-positive cocci. Taking this into consideration, the pharmacokinetics and pharmacodynamics shown in healthy volunteers suggest that with the use of standard doses of the various fluoroquinolones, an optimal AUCfree/MIC ratio for Gram-negative bacteria may be ensured with a minimum inhibitory concentration (MIC) <0.25-0.5 mg/L and for Gram-positive bacteria with an MIC <0.5-1 mg/L. The need to increase the dosage, or to combine them with other antibiotics is therefore recognized, when it is necessary to ensure adequate coverage of intermediately sensitive microorganisms (MIC 1-2 mg/L). In addition, patients recovered in the ICU often present some peculiar pathophysiological conditions that increase the distribution volume and/or the renal clearance of the drug. Thus it is likely that in this situation it would be reasonable to increase daily dosages, independent of the in vitro pattern of drug sensitivity (e.g. 500 mg b.i.d. for levofloxacin). Data from various clinical and pharmacological studies suggesting a potential role for fluoroquinolones both in monotherapy and combination therapy in the treatment of different clinically severe conditions are presented and discussed. This offers the dual opportunity to evaluate the role of quinolones as an alternative to aminoglycosides in combination with a beta-lactam and, at the same time, to consider their use in a periodic rotation program of anti-Gram-negative antibiotic therapy when there is a high risk of resistance selection, such as in the ICU. In conclusion, the role of fluoroquinolones in the treatment of multiple infectious diseases, such as bacteremia/sepsis, pneumonia and severe urinary tract infections in an environment such as the ICU is growing stronger, while there are convincing data indicating that these molecules might play a role in the treatment of meningitis in the near future
Principles of Pharmacodynamics and Pharmacokinetics of Drugs Used in Extracorporeal Therapies
No full textAntibiotic therapy in hematological neutropenic patients: what is the news?
No full textBacterial infection is a very common complication in hematological neutropenic patients whose treatment is extremely challenging for several reasons. First, they are frequently caused by resistant pathogens (multidrug resistant (MDR)), and this may limit the availability of effective therapeutic weapons. Second, these patients often present peculiar pathophysiological conditions that may alter the pharmacokinetic behavior of antimicrobials, and this may explain the need for a new administration schedule and new dosing regimens of antibiotics in this setting. In an era in which there are only few new therapeutic weapons for the treatment of MDR bacterial infections, while advocating for new drugs, what could be effectively done nowadays is to increase the knowledge on appropriateness of the use of currently available drugs to improve clinical outcome and to preserve their activity
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