Search results for "Dosing"

Population Pharmacokinetics of Palbociclib in aReal-World Situation

2021

Palbociclib is an oral cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Its metabolism profile is associated with an important interpatient variability. We performed a population pharmacokinetics study of palbociclib in women routinely followed in a cancer center. One hundred and fifty-one samples were analyzed. The sampling times after administration ranged from 0.9 to 75 h and the samples were taken between 1 and 21 days after the beginning of the palbociclib cycle. Palbociclib was determined using a validated mass spectrometry method. The best model that described the concentrat…

Dosing of caspofungin based on a pharmacokinetic/pharmacodynamic index for the treatment of invasive fungal infections in critically ill patients on …

2017

Abstract Introduction The study objective was to evaluate the efficacy of different dosages of caspofungin in the treatment of invasive candidiasis and aspergillosis, in relation to the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment, using modelling and Monte Carlo simulations in critically ill adult patients on continuous haemodiafiltration. Methods Critically ill adult patients on continuous venovenous haemodiafiltration treated with caspofungin were analysed. A population PK model was developed. Four caspofungin dosing regimens were simulated: the licensed regimen, 70 mg/day, 100 mg/day or 200 mg/day. A PK/PD target was defined as the ratio between the area unde…

The Role of Mathematical Models in Immuno-Oncology: Challenges and Future Perspectives

2021

Immuno-oncology (IO) focuses on the ability of the immune system to detect and eliminate cancer cells. Since the approval of the first immune checkpoint inhibitor, immunotherapies have become a major player in oncology treatment and, in 2021, represented the highest number of approved drugs in the field. In spite of this, there is still a fraction of patients that do not respond to these therapies and develop resistance mechanisms. In this sense, mathematical models offer an opportunity to identify predictive biomarkers, optimal dosing schedules and rational combinations to maximize clinical response. This work aims to outline the main therapeutic targets in IO and to provide a description …

Prophylaxis In Congenital Factor VII Deficiency, Indications, Efficacy and Safety: Results of the STER

2010

Abstract Abstract 665 Introduction Prophylaxis is considered a difficult endeavour in FVII deficiency, especially because of the very short FVII zymogen and FVIIa half-lives, mainly in childhood. The Seven Treatment Evaluation Registry (STER, www.targetseven.org) is a prospective observational, multi-centre, web-based registry concerned with the evaluation of treatments for spontaneous bleeding episodes, surgery and prophylaxis in patients with FVII deficiency. As regards prophylaxis, STER provides the frame for a structured and detailed data capture aiming at: a) identifying patients in whom prophylaxis is advisable, b) defining clinical settings in which prophylaxis is necessary and c) de…

208: Impact of posaconazole (POS) vs fluconazole (FLU) on cyclosporine (CsA) and tacrolimus (TAC) dosing in hematopoietic stem cell transplant (HSCT)…

2007

Factors responsible for interindividual differences in the dose requirement of phenprocoumon

1987

The total and unbound plasma concentrations of phenprocoumon and the prothrombin complex activity were determined in 51 patients on phenprocoumon. A 7-fold difference in the dosing rate (10-70 micrograms/kg/day) was required to maintain the prothrombin complex activity at 11-30% of normal. The variation in dosing requirement was mainly due to interindividual differences in the intrinsic clearance of phenprocoumon and only to a minor degree to differences in sensitivity to it. On average patients with myocardial infarction required only 2/3 of the daily dose of phenprocoumon of post cardiac surgery patients and patients with thrombosis and emboli. That difference appeared to be due to higher…

A comparative study of the population pharmacokinetics of gentamicin and amikacin in newborn patients

1993

SUMMARY The population kinetics of gentamicin and amikacin were studied comparatively in newborn patients with a similar range of gestation age (37.9 ± 2.9 and 36.7 ± 3.6 weeks), postnatal age (13.8 ± 7.4 and 16.7 ± 7 days) and weight (2.85 ± 0.57 and 2.72 ± 0.75 kg), undergoing routine therapeutic monitoring of their serum levels. Individual kinetic analysis of serum drug levels was done using a single-compartment model. The population model employed assumes the existence of residual variability in the serum concentrations and interindividual variability in the pharmacokinetic parameters. The clearance and the apparent distribution volume were calculated for each patient using a two-stage …

Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

2013

The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolim…

Impact of nutritional status on the oral bioavailability of leucine administered to rats as part of a standard enteral diet.

2010

Summary Background To investigate the absorption and relative bioavailability of leucine administered orally as part of an enteral diet in well and malnourished animals. Methods Two groups – RN (regular nutrition) and PCR (protein-calorie restricted) – were fed with different diets for 23–25 days. Rats from each group were assigned randomly to one of three treatments (water, T-Diet Plus Standard ® (problem) or Isosource ST ® (reference)) administered in single ( N  = 76) or multiple ( N  = 39) doses. Blood samples were assayed for leucine content. Area under the curve (AUC) was calculated by non-compartmental analysis. Log-transformed AUC(s) were statistically compared by analysis of varian…

Optimised versus standard dosing of vancomycin in infants with Gram-positive sepsis (NeoVanc): a multicentre, randomised, open-label, phase 2b, non-i…

2022

Summary Background Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms. Methods NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged …