Variability of mycophenolic acid elimination in the renal transplant recipients-population pharmacokinetic approach

© 2015 Informa Healthcare USA, Inc. The aim of this study was to develop a population pharmacokinetic (PK) model for clearance of mycophenolic acid (MPA) in adult renal transplant recipients, to quantify the PK parameters and the influence of covariates on the MPA pharmacokinetic parameters. Parameters associated with plasma concentrations of MPA at steady-state were analyzed in 70 renal transplant recipients (mean age 42.97 years; mean total body weight 75.33kg) using nonlinear mixed-effect modeling (NONMEM). Characteristics of patients screened for influence on the pharmacokinetic parameters were gender, age, body weight, time after transplantation, whether the patient was diagnosed as having diabetes mellitus, organ source (living or deceased donor), biochemical parameters and co-therapy (tacrolimus, cyclosporine, prednisolone, omeprazole, bisoprolol, carvedilol, nifedipine). A validation set of 25 renal transplant recipients was used to estimate the predictive performance of population pharmacokinetic model. Typical mean value of MPA oral clearance, estimated by base model (without covariates) was 0.741Lh-1. During population modeling, the full model showed that clearance of the MPA was significantly influenced by age, total daily dose of MPA, creatinine clearance, albumin level, status and gender of a donor, and the nifedipine and tacrolimus co-therapy. In the final model, clearance of MPA was reported to be significantly influenced by age, total daily dose of MPA and thenifedipine co-therapy. The derived model describes adequately MPA clearance in terms of characteristics of our patients, offering basis for individual pharmacotherapy approach

Population pharmacokinetics of 25-hydroxy Vitamin D in non-elderly postmenopausal women

© 2019 Polish Pharmaceutical Society. All Rights Reserved. Vitamin D is one of the keys to bone health, and the serum levels of this vitamin are a major concern for postmenopausal women. The aims of this study were to develop a population pharmacokinetic (PPK) model for the clearance of 25-hydroxy vitamin D in non-elderly postmenopausal women and to identify the factors which have a significant influence on its clearance. The study population consisted of postmenopausal women who had been referred for evaluation of bone mineral density (BMD) by DEXA (dual-energy x-ray absorptiometry) scanner. The population pharmacokinetics modeling was conducted using the ADVAN 1 subroutine from a non-linear mixed effects (NONMEM) program, and thirty-two covariates were assessed. A total of 75 serum concentrations were obtained from the same number of postmenopausal women and used for PPK analysis. The mean value of the participantsí age was 57.92 ± 3.93 years and their body weight was 69.76 ± 11.49 kg. A wide range of 25-hydroxy vitamin D concentrations was observed (from 3.41 to 61.92 ng/mL) with a mean value of 26.19 ± 10.95 ng/mL. A total of 32 covariates were examined and preliminary results suggested the influence of six covariates on 25-hydroxy vitamin D clearance. In the final PPK model, however, only one covariate was shown to have a significant impact on the clearance value ñ the mean daily dietary intake dose of vitamin D (DD). These findings offer a preliminary basis on which to determine the level of vitamin D supplementation required by individual postmenopausal women. It could prove particularly important in achieving optimal serum levels of vitamin D in this vulnerable population

An inverse correlation between TNF alpha serum levels and heart rate variability in patients with heart failure

Background: Recent evidence indicates that chronic heart failure (CHF) is accompanied by both activation of the immune system and autonomic imbalance. There is a growing body of evidence that increased levels of proinflammatory cytokines and other inflammatory markers have important roles as mediators of disease progression and markers of mortality in patients with CHF. Objective: The aim of this study was to investigate connection between autonomic imbalance [obtained by analysis of heart rate variability (HRV)] and activation of the immune system [as measured by serum levels of tumor necrosis factor (TNF)-α] in patients with chronic heart failure. Materials and methods: This cross-sectional study included 21 patients with CHF and 8 age- and gender-matched healthy control subjects. We assessed HRV by 24-hour electrocardiographic Holter monitoring and measured serum levels of TNF-α using an enzyme-linked immunosorbent assay. Clinical assessment and echocardiography were also performed. Results: There was an inverse correlation between serum level of TNF-α and a time-domain parameter of HRV - SDNN (r= -0.542, p< 0.05). A similar result was found for HRV triangular index, a geometric measure of HRV (r= -0.556; p< 0.05). The correlation was stronger for subjects with a diabetes mellitus, females, and TNFA2 allele carriers (an A at position -308A). The pNN50, indirect marker of cardiac vagal activity, was not significantly associated with serum concentration of TNF-α. Conclusions: In conclusion, the results of the present study indicate that increased serum TNF-α level is significantly associated with reduced HRV indices, suggesting that activation of the immune system in patients with CHF is closely related to autonomic imbalance. © 2013 Japanese College of Cardiology

Amlodipine as an antiischemic drug is superior to long acting nitrates

European Society of Cardiology Guidelines cite results of meta-analysis that the use of calcium channel blockers results in fewer angina episodes per week vs. long-acting nitrates. Moreover, we listed 12 reasons more to prefer amlodipine over long-acting nitrates, especially in stable angina pectoris patients with arterial hypertension. It may be the way to decrease polypharmacy without loosing efficacy. Some important advantages of amlodipine versus long-acting nitrate(s) are: amlodipine also treats hypertension, it helps reducing hypertensive target organ damages (e.g. left ventricular hypertrophy) and prevents morning blood pressure surge. Moreover, amlodipine can be given once daily (which improves adherence), it produces neither tolerance nor rebound, it has less side effects

Do health reforms impact cost consciousness of health care professionals? Results from a Nation-wide survey in the Balkans

© 2016 Trakya University Faculty of Medicine. Background: Serbia, as the largest market of the Western Balkans, has entered socioeconomic transition with substantial delay compared to most of Eastern Europe. Its health system reform efforts were bold during the past 15 years, but their results were inconsistent in various areas. The two waves of global recession that hit Balkan economies ultimately reflected to the financial situation of healthcare. Serious difficulties in providing accessible medical care to the citizens became a reality. A large part of the unbearable expenses actually belongs to the overt prescription of pharmaceuticals and various laboratory and imaging diagnostic procedures requested by physicians. Therefore, a broad national survey was conducted at all levels of the healthcare system hierarchy to distinguish the ability of cost containment strategies to reshape clinician’s mindsets and decision-making in practice. Aims: Assessment of healthcare professionals’ judgment on economic consequences of prescribed medical interventions and evaluation of responsiveness of healthcare professionals to policy measures targeted at increasing cost-consciousness. Study Design: Cross-sectional study. Methods: A nationwide cross-sectional survey was conducted through a hierarchy of medical facilities across diverse geographical regions before and after policy action, from January 2010 to April 2013. In the middle of the observed period, the National Health Insurance Fund (RFZO) adopted severe cost-containment measures. Independently, pharmacoeconomic guidelines targeted at prescribers were disseminated. Administration in large hospitals and community pharmacies was forced to restrict access to high budget-impact medical care. Economic Awareness of Healthcare Professionals Questionnaire–29 (EAHPQ-29), developed in Serbian language, was used in face-to-face interviews. The questionnaire documented clinician’s attitudes on: Clinical-Decision-Makingbetween- Alternative-Interventions (CDMAI), Qualityof- Health-Care (QHC), and Cost-Containment-Policy (CCP). The authors randomly and anonymously recruited 2000 healthcare experts, with a total of 1487 responding; after eliminating incomplete surveys, 649 participants were considered before and 651 after policy intervention. Results: Dentists (1.195±0.560) had a higher mean CDMAI score compared to physicians (1.017±0.453). Thesurgical group compared to the internist group had a higher total EAHPQ-29 score, CCP score and CDMAI score. Policy intervention had a statistically significant negative impact on the QHC score (F=4.958; df=1; p=0.027). There was no substantial impact of policy interventions on professional behavior and judgment with regard to the CDMAI, CCP, and total EAHPQ-29 scores. Conclusion: Although cost savings were forcibly imposed in practice, the effects on clinical decision-making weremodest. Clinicians’ perceptions of quality of medical care were explained in a less effective manner due to the severely constrained resources allocated to the providers. This pioneering effort in the Balkans exposes the inefficiency of current policies to expand clinicians’ cost consciousness

Polyphenolic profile of the fruits grown in Serbia

Polyphenolic compounds are known bioactive phytochemicals widely found in all plants as secondary metabolites. Many scientific papers have shown that they are very good markers for the assessment of botanical and geographical origin of several types of food. Thanks to favorable geographical and climatic conditions, Serbia has a very good prerequisite for the cultivation of various fruits. Well-favored soil characteristics, sunlight, and moisture significantly contribute to the accumulation of a lot of phytochemicals in ripe fruit, so the taste is fuller and aromatic, making the consumption of fruit in fresh forms most effective. Among others, Serbia has a long tradition in the production of grapes, plums, apples, pears, and various berries. Fruits growing in Serbia are very important products for both local and world markets. This paper gives an overview of methods most frequently used for extraction and identification of fruit polyphenolics. It includes a review of the literature describing the characterization of the polyphenolic profile of different fruits grown in Serbia. In addition, for certain types of fruits, the chemical analysis of the leaves of studied fruits was provided. © 2018 American Chemical Society