Introductory Chapter: Linkages between Pharmacokinetics and Adverse Effects of Drugs

Malangu, Ntambwe

doi:10.5772/intechopen.76511

Cited by 7 publications

(4 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 71 If the liver (a digestive system) functions less optimally, drugs are not readily metabolized and excreted and this leads to many drugs staying in the system much longer, the net result being the prolongation of pharmacodynamic effects and occurrence of ADEs. 73 …”

Section: Discussionmentioning

confidence: 99%

Adverse Drug Events and Contributing Factors Among Hospitalized Adult Patients at Jimma Medical Center, Southwest Ethiopia: A Prospective Observational Study

Sahilu

Getachew

Melaku

et al. 2020

Current Therapeutic Research

View full text Add to dashboard Cite

Background Adverse drug events (ADEs) are common complications of clinical care resulting in significant morbidity, mortality, and high clinical expenditure. Population-level estimates of inpatient ADEs are limited in Ethiopia. Objective This study aimed to assess the incidence, contributing factors, severity, and preventability of ADEs among hospitalized adult patients at Jimma Medical Center, Ethiopia. Methods A prospective observational study design was conducted among hospitalized adult patients at tertiary hospital in Ethiopia. A structured data collection tool was prepared from relevant literatures for data collection. Data were analyzed using statistical software. Logistic regression was performed to identify factors contributing to ADE occurrence. P values < 0.05 were considered statistically significant. Results A total of 319 patients were included with follow-up period of 5667 person-days. About 50.5% were women. The mean (SD) age of patients was 43 (17.6) years. One hundred sixteen ADEs were identified with the incidence of 36.4 (95% CI, 30.1–43.6) per 100 admissions and 20.5 (95% CI, 16.9–24.6) per 1000 person-days. Antituberculosis agents (adjusted odds ratio [aOR] = 2.52; 95% CI, 1.06–5.98; P = 0.036), disease of the circulatory system (aOR = 2.67; 95% CI, 1.46–4.89; P = 0.001), disease of the digestive system (aOR = 2.84; 95% CI, 1.45–5.57; P = 0.002), being on medication during admission (aOR = 3.09; 95% CI, 1.77–5.41; P < 0.001), and hospital stay more than 2 weeks (aOR = 3.93; 95% CI, 1.39–11.12; P = 0.010) were independent predictors of ADE occurrence. Conclusions One in every 4 patients admitted to the hospital experienced ADEs during their hospital stay. Most ADEs were moderate in severity. About two-thirds of the ADEs identified were deemed probably or definitely preventable. Therefore, it is high time to reinforce large-scale efforts to redesign safer, higher quality health care systems to adequately tackle the problem.

show abstract

Section: Discussionmentioning

confidence: 99%

Adverse Drug Events and Contributing Factors Among Hospitalized Adult Patients at Jimma Medical Center, Southwest Ethiopia: A Prospective Observational Study

Sahilu

Getachew

Melaku

et al. 2020

Current Therapeutic Research

View full text Add to dashboard Cite

show abstract

“…The parameters analyzed through the measurement of medication blood concentration to determine its fate in the body are the processes of absorption, distribution, metabolism, and excretion (ADME) [ 50 ]. Acting together, these processes determine the onset, duration, and intensity of a drug’s effect; therefore, a comprehensive understanding of PK is essential in planning medication treatment regimen (e.g., dosing and timing of administration) and predicting the risk of possible adverse reactions [ 51 ]. Considering this, the regulatory agencies provide guidelines that require non-clinical and clinical PK assessment for the marketing authorization of most medicinal products.…”

Section: Pharmacokinetic Considerations Of Mrna Vaccinesmentioning

confidence: 99%

Updated Considerations for the Immunopharmacological Aspects of the “Talented mRNA Vaccines”

Perrotta,

Fenizia,

Carnovale

et al. 2023

Vaccines

View full text Add to dashboard Cite

Messenger RNA (mRNA) vaccines belong to a new class of medications, RNA therapeutics, including both coding and non-coding RNAs. The use of mRNA as a therapy is based on the biological role of mRNA itself, namely its translation into a functional protein. The goal of mRNA vaccines is to produce a specific antigen in cells to elicit an immune response that might be prophylactic or therapeutic. The potential of mRNA as vaccine has been envisaged for years but its efficacy has been clearly demonstrated with the approval of COVID-19 vaccines in 2021. Since then, mRNA vaccines have been in the pipeline for diseases that are still untreatable. There are many advantages of mRNA vaccines over traditional vaccines, including easy and cost-effective production, high safety, and high-level antigen expression. However, the nature of mRNA itself and some technical issues pose challenges associated with the vaccines’ development and use. Here we review the immunological and pharmacological features of mRNA vaccines by discussing their pharmacokinetics, mechanisms of action, and safety, with a particular attention on the advantages and challenges related to their administration. Furthermore, we present an overview of the areas of application and the clinical trials that utilize a mRNA vaccine as a treatment.

show abstract

“…This is largely due to the limitations and inconsistencies of preclinical screening models. Exploring this, hepatotoxicity has been cited as the most common causative factor for withdrawal of post marketed drugs 5 , 6 . When using immortalized or primary cell cultures as surrogates for their in vivo counterparts it is important to adequately characterize each model system before being able to make reliable biological inferences.…”

Section: Introductionmentioning

confidence: 99%

Continual proteomic divergence of HepG2 cells as a consequence of long-term spheroid culture

Ellero

Bout

Vlok

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Three-dimensional models are considered a powerful tool for improving the concordance between in vitro and in vivo phenotypes. However, the duration of spheroid culture may influence the degree of correlation between these counterparts. When using immortalised cell lines as model systems, the assumption for consistency and reproducibility is often made without adequate characterization or validation. It is therefore essential to define the biology of each spheroid model by investigating proteomic dynamics, which may be altered relative to culture duration. As an example, we assessed the influence of culture duration on the relative proteome abundance of HepG2 cells cultured as spheroids, which are routinely used to model aspects of the liver. Quantitative proteomic profiling of whole cell lysates labelled with tandem-mass tags was conducted using liquid chromatography-tandem mass spectrometry (LC–MS/MS). In excess of 4800 proteins were confidently identified, which were shared across three consecutive time points over 28 days. The HepG2 spheroid proteome was divergent from the monolayer proteome after 14 days in culture and continued to change over the successive culture time points. Proteins representing the recognised core hepatic proteome, cell junction, extracellular matrix, and cell adhesion proteins were found to be continually modulated.

show abstract

Introductory Chapter: Linkages between Pharmacokinetics and Adverse Effects of Drugs

Cited by 7 publications

References 75 publications

Adverse Drug Events and Contributing Factors Among Hospitalized Adult Patients at Jimma Medical Center, Southwest Ethiopia: A Prospective Observational Study

Adverse Drug Events and Contributing Factors Among Hospitalized Adult Patients at Jimma Medical Center, Southwest Ethiopia: A Prospective Observational Study

Updated Considerations for the Immunopharmacological Aspects of the “Talented mRNA Vaccines”

Continual proteomic divergence of HepG2 cells as a consequence of long-term spheroid culture

Contact Info

Product

Resources

About