Atazanavir and darunavir total concentrations (drug bound to plasma proteins plus unbound drug) progressively decrease during pregnancy. This pharmacokinetic variation leads physicians to recommend increasing doses. Conversely, the unbound concentration (Cu), i.e. the pharmacologically active form of the drug, remains unchanged. The explanation of this desynchronization lies in the fact that the clearance of the unbound form, corresponding to the intrinsic metabolic capacity of the hepatocytes, is the only factor driving Cu, and is constant during pregnancy. The attention of HIV physicians should be attracted to this aspect of pharmacokinetics, which is often incompletely understood and could lead to inadequate dose adjustment, which could then cause overexposure of the foetus for many months, with unknown consequences.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jac/dkx176 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Translating PK-PD principles into improved methodology for clinical trials which compare intermittent with prolonged infusion of beta-lactam antibiotics.
Clin Infect Dis
January 2025
Professor of Medicine, Director, Institute for Therapeutic Innovation at University of Florida, Orlando, FL, USA.
Based on the fact that beta-lactam antibiotics demonstrate time-dependent killing, different dosing strategies have been implemented to increase the time that free (f) (unbound) antibiotic concentrations remain above the Minimal Inhibitory Concentration (MIC), including prolonged and continuous infusion. Multiple studies have been performed that compared continuous with traditional intermittent infusion to improve outcomes in patients with severe sepsis and/or septic shock. These studies have yielded inconsistent results for patients as measured by clinical response to treatment and mortality due to heterogeneity of included patients, pathogens, dosing strategies and the absence of Therapeutic Drug Monitoring (TDM).
View Article and Find Full Text PDFDose Evaluation and Optimization of Amoxicillin in Children Treated for Lyme Disease.
J Clin Pharmacol
January 2025
Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Amoxicillin is commonly used to treat erythema migrans in the first stage of Lyme disease in children, with a recommended dose of 50 mg/kg/day, administered three times a day (q8h). This model-based simulation study aimed to determine whether splitting the same daily dose into two administrations (q12h) would provide comparable drug exposure. A pharmacokinetic model suitable for a pediatric population (age: 1 month to 18 years, weight: 4-80 kg) was selected through a literature review.
View Article and Find Full Text PDFEffect of Target-Mediated Disposition on Iptacopan Clinical Pharmacokinetics in Participants with Normal or Impaired Hepatic Function.
Clin Pharmacol Ther
January 2025
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Iptacopan, a first-in-class complement factor B inhibitor acting proximally in the alternative complement pathway, has been shown to be safe and effective for patients with complement-mediated diseases. Iptacopan selectively binds with high affinity to factor B, a soluble, plasma-based, hepatically produced protein. Factor B is abundant in the circulation but can be saturated at the iptacopan clinical dose of 200 mg twice daily.
View Article and Find Full Text PDFThe clinical breakpoint for a drug-pathogen combination reflects the drug susceptibility of the pathogen wild-type population, the location of the infection, the integrity of the host immune response, and the drug-pathogen pharmacokinetic (PK)/pharmacodynamic (PD) relationship. That PK/PD relationship, along with the population variability in drug exposure, is used to determine the probability of target attainment (PTA) of the PK/PD index at a specified minimum inhibitory concentration (MIC) for a selected target value. The PTA is used to identify the pharmacodynamic cutoff value (CO), which is one of the three components used to establish the clinical breakpoint.
View Article and Find Full Text PDFMechanistic insights into HPV-positivity in non-smokers and HPV-negativity in smokers with head and neck cancer.
Front Oncol
January 2025
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Schleswig-Holstein, Kiel, Germany.
Introduction: Several aspects of the involvement of HPV in the pathogenesis of HPV-associated diseases remain poorly understood including mechanistic aspects of infection and the question of why the majority of HPV-positive HNSCC-patients are non-smokers, whereas HPV-negatives are smokers. Our previous research, based on 1,100 patient samples, hypothesized an explanation for this phenomenon: Smoking induces upregulation of a mucosal protective protein (SLPI), which competes with HPV for binding to Annexin A2 (AnxA2), pivotal for HPV cell entry. Here we investigate the mechanistic aspects of our hypothesis using transfection assays.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!