177,085 research outputs found
Clinical Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants in Patients with Renal Failure
No full textRem tene, verba sequentur - primi dati sull'attività delle U.O. di Pronto Soccorso di Bassano del Grappa e Asiago
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Column liquid chromatographic determination of prajmalium in plasma and urine by direct sample injection
No full textAssessing the relative potency of (S)- and (R)-warfarin with a new PK-PD model, in relation to VKORC1 genotypes
No full textPurpose. The purpose of this study is to develop a new pharmacokinetic-pharmacodynamic (PK-PD) model to characterise the contribution of (S)- and (R)-warfarin to the anticoagulant
effect on patients in treatment with rac-warfarin.
Methods. Fifty-seven patients starting warfarin (W) therapy were studied, from the first dose and during chronic treatment at INR stabilization. Plasma concentrations of (S)- and (R)-W and INRs were measured 12, 36 and 60 h after the first dose and at steady state 12–14 h after dosing. Patients were also genotyped for the G>A VKORC1 polymorphism. The PK-PD model assumed a linear relationship between W enantiomer concentration and INR and included a scaling factor k to account for a different potency of (R)-W. Two parallel compartment chains with different transit times (MTT1 and MTT2) were used to model the delay in the Weffect. PD parameters were estimated with the maximum likelihood approach.
Results. The model satisfactorily described the mean timecourse of INR, both after the initial dose and during longterm treatment. (R)-W contributed to the rac-Wanticoagulant effect with a potency of about 27% that of (S)-W. This effect was independent of VKORC1 genotype. As expected, the slope of the PK/PD linear correlation increased stepwise from
GG to GA and from GA to AAVKORC1 genotype (0.71, 0.90 and 1.49, respectively).
Conclusions. Our PK-PD linear model can quantify the partial pharmacodynamic activity of (R)-W in patients contemporaneously exposed to therapeutic (S)-W plasma levels. This concept may be useful in improving the performance of future algorithms aiming at identifying the most appropriateWmaintenance dose
Renal clearance of N-1-Methylnicotinamide is a marker of liver dysfunction in cirrhosis
No full textBACKGROUND/AIMS: Data have appeared suggesting that an impairment of renal tubular secretion is present in liver cirrhosis, even in the absence of a clinically evident renal dysfunction. To address this question, we evaluated the renal clearance of N(1)-methylnicotinamide (NMN), a marker of the renal secretory function, in healthy subjects and patients with liver cirrhosis of increasing severity, but with a normal glomerular filtration rate.
METHODS: The renal clearances of endogenous NMN, inulin, and creatinine were measured in 14 normal subjects and in two groups of age-matched cirrhotic patients (10 Child A and 10 Child C). In 6 subjects, 2 per group, the concentration dependence of the NMN clearance was also studied, following an oral nicotinamide load.
RESULTS: Contrary to expectations, the renal NMN clearance increased in cirrhotic patients, in relation to the severity of liver disease (r = 0.83 with Pugh's score; p < 0.001). The NMN-to-inulin clearance ratio increased from a control value of 2.2 +/- (SD) 0.4 to 3.1 +/- 0.2 and 5.2 +/- 0.9 in Child A and Child C cirrhotics, respectively (p < 0.001 for all comparisons), indicating that NMN was completely cleared from plasma in the latter patients. Consistently, the analysis of the concentration dependence of the renal NMN clearance revealed the presence of a carrier-mediated reabsorption which apparently was no longer operating in the decompensated patients. Discriminant analysis showed that renal NMN clearance, and NMN-to-creatinine and NMN-to-inulin clearance ratios could all distinguish between the three study groups, with sensitivities and specificities equal or greater than 90%.
CONCLUSIONS: Contrary to previous proposals, NMN is not a probe of general validity for renal tubular secretion. In particular, due to an imbalance between secretion and reabsorption, its renal clearance in liver cirrhosis cannot be used to determine the degree of tubular secretion of which an individual is capable. However, renal NMN clearance appears to be a very sensitive marker of the severity of liver dysfunction in cirrhosis. The potentialities of this renal parameter as a diagnostic and prognostic test in liver cirrhosis deserve further study
Famiglia Violenza Pari Opportunità visti con gli occhi di bimbi e adolescenti
No full textIndagine “pilota” su alunni e studenti della scuola primaria, secondaria di I° grado e di II° grado (per quest’ultima categoria Licei e Istituti tecnici e professionali), testata su due provincie della Regione Veneto, Vicenza posta sulla direttrice mediana della regione e Rovigo, più piccola e ai margini, prevedendo per entrambe il coinvolgimento di Istituti scolastici collocati tanto nel capoluogo, quanto nel territorio provinciale.
Essa mira a individuare non la realtà dei soggetti che sono un “universo in formazione”, ma i riflessi di un fenomeno sulle loro coscienze
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