Population pharmacokinetics of vancomycin in adult patients with long bones’ fractures

Vancomycin is a tricyclic glycopeptide antibiotic, mostly used in the treatment of severe staphylococcal and enterococcal infections, especially in orthopedic surgery. The purpose of this analysis was to develop a population pharmacokinetic (PPK) model of vancomycine in hospitalized patients with bone fractures and identify important factors which influence its clearance (CL). A total of ninety-nine measurements of vancomycin serum concentrations were used in our population modeling. A two-compartment model was applied to describe the pharmacokinetics of vancomycin using subroutines ADVAN3 and TRANS4. The study population included patients of both sexes, with the mean age of 62.12±14.69 years and body weight of 80.32±12.44kg. Vancomycin was administered as intravenous infusion with average daily dose of 1772.73±521.34mg. Out of twenty different factors evaluated in the study (including demo-graphic, clinical and laboratory data), only daily dose of vancomycin (DD) and co-medication with piperacillin/tazobactam (PT) showed significant effect on clearance of vancomycin. The final model was described by the following equation: CL (l/h) = 0.03 + 0.000468 x DD + 0.675 x PT. Bootstrapping was used for validation of the final model. In conclusion, the main causes of variability in the clearance of vancomycin among adult patients with bone fractures are daily dose of vancomycin and co-medication with piperacillin/tazobactam

CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed

Antimicrobial treatment of erysipelatoclostridium ramosum invasive infections: A systematic review

The aim of this systematic review was to determine the causal role of Erysipelatoclostridium ramosum in specific invasive infections in humans, and to assess the clinical outcome of antibiotic therapy used to treat them. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with a systemic inflammatory response syndrome (SIRS) due to E. ramosum isolated from body fluids or tissues in which it is not normally present. Only reports identifying E. ramosum as the only microorganism isolated from a patient with SIRS were included. This systematic review included 15 studies reporting 19 individual cases in which E. ramosum caused invasive infections in various tissues, mainly in immunocompromised patients. E. ramosum was most often isolated by blood cultures and identified by specific biochemical tests. Severe infections caused by E. ramosum were in most cases effectively treated with antibiotics, except in two patients, one of whom died. More than one isolate of E. ramosum exhibited 100% susceptibility to metronidazole, amoxicillin/clavulanate and piperacillin/tazobactam. On the other hand, individual resistance of this bacterium to penicillin, ciprofloxacin, clindamycin, imipenem and ertapenem was reported. This systematic review confirmed the clinical relevance of E. ramosum as a cause of a number of severe infections mainly in immunocompromised inpatients. Metronidazole and meropenem appear to be the antibiotics of choice that should be used in combination or as monotherapy to treat E. ramosum infections, depending on the type and severity of the infection

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

Screening for Anxiety Disorders Among Schoolchildren with Asthma

The aim of this study was to perform screening for anxiety disorders among children with asthma and to reveal factors associated with general anxiety disorder and its specific forms

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