journal article
Download Only Collection
Home
Song, Tanya; Wang, Yunfei; Silverglate, Bret David; Grossberg, George T.
doi: 10.1080/17425255.2024.2357637pmid: 38758223
Introduction Donanemab is a humanized monoclonal antibody that significantly reduces cerebral amyloid plaques in Alzheimer’s Disease (AD). It can delay disease progression and cognitive decline, making it one of the most promising disease-modifying treatments in the current treatment landscape. Areas Covered This paper covers the current literature available on pharmacokinetics, pharmacodynamics, safety, and tolerability of donanemab. Publications from PubMed and Google were reviewed. A summary of regulatory approvals and current clinical data is also provided. Expert Opinion/Commentary Donanemab as a therapy for AD has more effective disease-modifying effects compared to lecanemab. Donanemab appears generally well-tolerated; however, it may have higher rates of severe side effects, such as amyloid-related imaging abnormalities (ARIA), that could lead to death. Guidelines for frequency of MRI monitoring for ARIA/safety are pending but will be integral to determining its use. Despite some limitations, donanemab is expected to receive FDA approval, giving clinicians access to another disease-modifying drug. Overall, more data is needed about donanemab, especially relating to safety, efficacy, cost, and integration with other treatments, but its development signifies progress in AD treatment.
Todorović, Zoran; Dragović, Gordana; Lukić, Relja
doi: 10.1080/17425255.2024.2353762pmid: 38738389
Introduction To prevent mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV) during pregnancy, the appropriate dosing regimens of antiretroviral (ARV) drugs need to be determined. Reliable data about pharmacokinetic (PK) characteristics of ARVs from randomized clinical trials (RCTs) are lacking, and post-marketing observational studies may offer valuable, but sometimes insufficient data, especially in pregnant people living with HIV (PLWHIV). This review article is focused PK and toxicological considerations affecting ARV dosing in pregnant PLWHIV. Areas covered In our search, we included studies focused on PKs of ARVs in pregnancy available on PubMed, abstracts from recent global conferences and data from modeling studies. There are no significant changes in PKs of nucleoside/nucleotide reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors throughout pregnancy. In contrast, the PKs of PIs and INSTIs are more variable, especially in the second and third trimesters. Expert opinion Pregnant women are left out of RCTs. To the greatest extent possible, future research should include pregnant persons in RCTs, including PK studies, strictly considering maternal and fetal safety. Alternative innovative approaches/models need to be developed to obtain reliable data about rational pharmacotherapy of ARVs in the effective PMTCT of HIV, with maximum safety.
Eltanameli, Bassma; Piñeiro-Llanes, Janny; Cristofoletti, Rodrigo
doi: 10.1080/17425255.2024.2366390pmid: 38850058
Introduction Recent years have witnessed remarkable progress in the development of cell-based in vitro models aimed at predicting drug permeability, particularly focusing on replicating the barrier properties of the blood-brain barrier (BBB), intestinal epithelium, and lung epithelium. Area covered This review provides an overview of 2D in vitro platforms, including monocultures and co-culture systems, highlighting their respective advantages and limitations. Additionally, it discusses tools and techniques utilized to overcome these limitations, paving the way for more accurate predictions of drug permeability. Furthermore, this review delves into emerging technologies, particularly microphysiological systems (MPS), encompassing static platforms such as organoids and dynamic platforms like microfluidic devices. Literature searches were performed using PubMed and Google Scholar. We focus on key terms such as in vitro permeability models, MPS, organoids, intestine, BBB, and lungs. Expert Opinion The potential of these MPS to mimic physiological conditions more closely offers promising avenues for drug permeability assessment. However, transitioning these advanced models from bench to industry requires rigorous validation against regulatory standards. Thus, there is a pressing need to validate MPS to industry and regulatory agency standards to exploit their potential in drug permeability prediction fully. This review underscores the importance of such validation processes to facilitate the translation of these innovative technologies into routine pharmaceutical practice.
Vasconez Martinez, Mateo Gabriel; Frauenlob, Martin; Rothbauer, Mario
doi: 10.1080/17425255.2024.2362183pmid: 38832686
Introduction Advances in the accessibility of manufacturing technologies and iPSC-based modeling have accelerated the overall progress of organs-on-a-chip. Notably, the progress in multi-organ systems is not progressing with equal speed, indicating that there are still major technological barriers to overcome that may include biological relevance, technological usability as well as overall accessibility. Areas covered We here review the progress in the field of multi-tissue- and body-on-a-chip pre and post- SARS-CoV-2 pandemic and review five selected studies with increasingly complex multi-organ chips aiming at pharmacological studies. Expert opinion We discuss future and necessary advances in the field of multi-organ chips including how to overcome challenges regarding cell diversity, improved culture conditions, model translatability as well as sensor integrations to enable microsystems to cover organ–organ interactions in not only toxicokinetic but more importantly pharmacodynamic and -kinetic studies.
Orhan, Adile; Nguyen, Carolyn; Chan, Alexandre; Herrstedt, Jørn
doi: 10.1080/17425255.2024.2367593pmid: 38878283
Introduction Dopamine (D)2,3-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). Areas covered Eight D2,3-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects. Expert opinion Since the introduction of D2,3-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)3-RAs and neurokinin (NK)1-RAs have been developed. The classical D2,3-RAs are recommended in the prophylaxis of CINV from low emetic risk chemotherapy, but not as a fixed component of an antiemetic regimen for moderately or highly (HEC) emetic risk chemotherapy. D2,3-RAs are also used in patients with breakthrough nausea and vomiting. It should be emphasized, that most of these drugs are not selective for dopamine receptors. The multi-receptor targeting agent, olanzapine, is recommended in the prophylaxis of HEC-induced CINV as part of a four-drug antiemetic regimen, including a 5-HT3-RA, dexamethasone and a NK1-RA. Olanzapine is the most effective agent to prevent chemotherapy-induced nausea. Side effects differ among various D2,3-RAs. Metopimazine and domperidone possess a low risk of extrapyramidal side effects. Domperidone and metoclopramide are prokinetics, whereas metopimazine delays gastric emptying and haloperidol does not influence gastric motility. Many D2,3-RAs increase the risk of prolonged QTc interval; other side effects include sedation and orthostatic hypotension.
Gasperoni, Lorenzo; Giunta, Emilio Francesco; Montanari, Daniela; Masini, Carla; De Giorgi, Ugo
doi: 10.1080/17425255.2024.2353749pmid: 38778707
Introduction The therapeutic scenario of metastatic hormone-sensitive prostate cancer (mHSPC) has dramatically changed in recent years, with the approval of new-generation Androgen Receptor Signaling Inhibitors (ARSIs), in combination with the androgen deprivation therapy (ADT), which was the previous standard of care. Despite showing a similar clinical efficacy, ARSIs, all of which are administered orally, are different in terms of pharmacokinetic and drug-drug interactions (DDIs). Areas covered This review covers the main pharmacokinetic characteristics of ARSIs that have been approved for the first-line therapy of mHSPC patients, underlying the differences among these molecules and focusing on the known or possible interactions with other drugs. Full-text articles and abstracts were searched in PubMed. Expert opinion Since prostate cancer occurs mainly in older age, comorbidities and the consequent polypharmacy increase the DDI risk in mHSPC patients who are candidates for ARSI. Waiting for new therapeutic options, in the absence of direct comparisons, pharmacokinetic knowledge is essential to guide clinicians in prescribing ARSI in this setting.
Okyar, Alper; Ozturk Civelek, Dilek; Akyel, Yasemin Kubra; Surme, Saliha; Pala Kara, Zeliha; Kavakli, İ. Halil
doi: 10.1080/17425255.2024.2356167pmid: 38753451
Introduction The 24-hour variations in drug absorption, distribution, metabolism, and elimination, collectively known as pharmacokinetics, are fundamentally influenced by rhythmic physiological processes regulated by the molecular clock. Recent advances have elucidated the intricacies of the circadian timing system and the molecular interplay between biological clocks, enzymes and transporters in preclinical level. Area covered Circadian rhythm of the drug metabolizing enzymes and carrier efflux functions possess a major role for drug metabolism and detoxification. The efflux and metabolism function of intestines and liver seems important. The investigations revealed that the ABC and SLC transporter families, along with cytochrome p-450 systems in the intestine, liver, and kidney, play a dominant role in the circadian detoxification of drugs. Additionally, the circadian control of efflux by the blood–brain barrier is also discussed. Expert opinion The influence of the circadian timing system on drug pharmacokinetics significantly impacts the efficacy, adverse effects, and toxicity profiles of various drugs. Moreover, the emergence of sex-related circadian changes in the metabolism and detoxification processes has underscored the importance of considering gender-specific differences in drug tolerability and pharmacology. A better understanding of coupling between central clock and circadian metabolism/transport contributes to the development of more rational drug utilization and the implementation of chronotherapy applications.
Kasten, Anne; Cascorbi, Ingolf
doi: 10.1080/17425255.2024.2362184pmid: 38809523
Introduction In addition to the well-established understanding of the pharmacogenetics of drug-metabolizing enzymes, there is growing data on the effects of genetic variation in drug transporters, particularly ATP-binding cassette (ABC) transporters. However, the evidence that these genetic variants can be used to predict drug effects and to adjust individual dosing to avoid adverse events is still limited. Areas covered This review presents a summary of the current literature from the PubMed database as of February 2024 regarding the impact of genetic variants on ABCG2 function and their relevance to the clinical use of the HMG-CoA reductase inhibitor rosuvastatin and the xanthine oxidase inhibitor allopurinol. Expert opinion Although there are pharmacogenetic guidelines for the ABCG2 missense variant Q141K, there is still some conflicting data regarding the clinical benefits of these recommendations. Some caution appears to be warranted in homozygous ABCG2 Q141K carriers when rosuvastatin is administered at higher doses and such information is already included in the drug label. The benefit of dose adaption to lower possible side effects needs to be evaluated in prospective clinical studies.
Jadav, Tarang; Rajput, Niraj; Kumar, Hemant; Behera, Santosh Kumar; Sengupta, Pinaki
doi: 10.1080/17425255.2024.2352462pmid: 38712502
Background Antiretrovirals have the potential to cause drug interactions leading to inefficacy or toxicity via induction of efflux transporters through nuclear receptors, altering drug concentrations at their target sites. Research Design and Methods This study used molecular dynamic simulations and qRT-PCR to investigate bictegravir’s interactions with nuclear receptors PXR and CAR, and its effects on efflux transporters (P-gp, BCRP, MRP1) in rat PBMCs. PBMC/plasma drug concentrations were measured using LC-MS/MS to assess the functional impact of transporter expression. Results Bictegravir significantly increased the expression of ABC transporters, with Car identified as a key mediator. This suggests that bictegravir’s influence on nuclear receptors could affect drug transport and efficacy at the cellular level. Conclusions Bictegravir activates nuclear receptors enhancing efflux transporter expression. Understanding these interactions is crucial for preventing drug–drug interactions and reducing toxicity in clinical use. Combining CAR antagonists with bictegravir may prevent drug resistance and toxicity. However, these findings are based on preclinical data and necessitate further clinical trials to confirm their applicability in clinical settings.
Showing 1 to 10 of 10 Articles