drug pharmacokinetics
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2022 ◽  
Vol 23 (2) ◽  
pp. 818
Author(s):  
Merel van Nuland ◽  
Tessa F. Ververs ◽  
Marnix G. E. H. Lam

The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population. This could potentially lead to underdosing and thus suboptimal treatment in obese patients, while it could also lead to drug toxicity due to high levels of radioactivity. In this review, relevant literature is summarized on radiopharmaceutical dosing and pharmacokinetic properties, and we aimed to translate these data into practical guidelines for dosing of radiopharmaceuticals in obese patients. For radium-223, dosing in obese patients is well established. Furthermore, for samarium-153-ethylenediaminetetramethylene (EDTMP), dose-escalation studies show that the maximum tolerated dose will probably not be reached in obese patients when dosing on MBq/kg. On the other hand, there is insufficient evidence to support dose recommendations in obese patients for rhenium-168-hydroxyethylidene diphosphonate (HEDP), sodium iodide-131, iodide 131-metaiodobenzylguanidine (MIBG), lutetium-177-dotatate, and lutetium-177-prostate-specific membrane antigen (PSMA). From a pharmacokinetic perspective, fixed dosing may be appropriate for these drugs. More research into obese patient populations is needed, especially in the light of increasing prevalence of obesity worldwide.


2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Ji-Won Seo ◽  
Kaiyu Fu ◽  
Santiago Correa ◽  
Michael Eisenstein ◽  
Eric A. Appel ◽  
...  

2021 ◽  
Vol 1 (2) ◽  
pp. 41-45
Author(s):  
Tan Andi ◽  
Tjahya Aryasa ◽  
Tjokorda Gde Agung Senapathi

Introduction: Chronic kidney disease (CKD) is marked by the presence of kidney damage (usually defined as estimated GFR < 60 mL/ min/1.73 m2) for 3 or more months, and it may be caused by a multitude of disease processes. Management of patients with CKD includes aggressive treatment of the underlying cause, pharmacologic therapy to delay disease progression and prevent complications, and preparation for hemodialysis as ESRD ensues. Case presentation: In this case report, a 48-year-old man with a pseudoaneurysms due to the insertion of a vascular access for hemodialysis, undergo repair pseudoaneurysms surgery under general anesthesia, at the Sanglah General Hospital, October 2020. The patient came with fully awareness, blood pressure 145/95 mmHg, heart rate 85 times per minute regular and oxygen saturation 97% with room air. Conclusion: General anesthesia in patients with CKD requires an understanding of the pathologic changes that accompany renal disease, co-existing medical conditions, and the impact of reduced renal function on drug pharmacokinetics.


Author(s):  
Ahizechukwu C. Eke

Abstract For many years, the medical community has relied in clinical practice on historic data about the physiological changes that occur during pregnancy. However, some newer studies have disputed a number of assumptions in these data for not being evidence-based or derived from large prospective cohort-studies. Accurate knowledge of these physiological changes is important for three reasons: Firstly, it facilitates correct diagnosis of diseases during pregnancy; secondly, it enables us to answer questions about the effects of medication during pregnancy and the ways in which pregnancy alters pharmacokinetic and drug-effects; and thirdly, it allows for proper modeling of physiologically-based pharmacokinetic models, which are increasingly used to predict gestation-specific changes and drug–drug interactions, as well as develop new knowledge on the mode-of-action of drugs, the mechanisms underlying their interactions, and any adverse effects following drug exposure. This paper reviews new evidence regarding the physiologic changes during pregnancy in relation to existing knowledge.


EMJ Diabetes ◽  
2021 ◽  
pp. 64-74
Author(s):  
Partha Pal ◽  
Subhodip Pramanik ◽  
Sayantan Ray

Gastrointestinal (GI) symptoms represent an important and often poorly appreciated reason of morbidity in diabetes mellitus. Diabetes can affect nearly all parts of the GI tract; however, data on the prevalence of ‘diabetic gastroenteropathy’ are inconsistent. The significance of disturbed GI motility in diabetes across the patient spectrum and pathophysiological basis also remain inadequately defined. Fluctuating glucose levels, altered drug pharmacokinetics, variable absorption of nutrients, and impaired quality of life are important consequences of GI dysfunction. Diabetic gastroparesis is the best characterised manifestation of GI motility disorder in diabetes. Since there is a poor correlation between subjective GI symptoms and objective motility findings, a diagnosis of delayed emptying in diabetes requires a proper measurement of gastric emptying. There are fewer studies on intestinal motility in diabetes than those on the stomach. Several established modalities exist for the assessment of gastroenteropathy but the lack of standardisation, exposure to radiation, advanced data interpretation, and high cost limit their widespread use. While existing therapeutic choices for the management of diabetic gastroenteropathy are suboptimal, many potential novel agents are in progress. Both endocrinology and gastroenterology specialties working together will facilitate screening and treating patients with diabetes and GI dysmotility.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qin Yu ◽  
Dongchun Ni ◽  
Julia Kowal ◽  
Ioannis Manolaridis ◽  
Scott M. Jackson ◽  
...  

AbstractABCG2 is a multidrug transporter that affects drug pharmacokinetics and contributes to multidrug resistance of cancer cells. In previously reported structures, the reaction cycle was halted by the absence of substrates or ATP, mutation of catalytic residues, or the presence of small-molecule inhibitors or inhibitory antibodies. Here we present cryo-EM structures of ABCG2 under turnover conditions containing either the endogenous substrate estrone-3-sulfate or the exogenous substrate topotecan. We find two distinct conformational states in which both the transport substrates and ATP are bound. Whereas the state turnover-1 features more widely separated NBDs and an accessible substrate cavity between the TMDs, turnover-2 features semi-closed NBDs and an almost fully occluded substrate cavity. Substrate size appears to control which turnover state is mainly populated. The conformational changes between turnover-1 and turnover-2 states reveal how ATP binding is linked to the closing of the cytoplasmic side of the TMDs. The transition from turnover-1 to turnover-2 is the likely bottleneck or rate-limiting step of the reaction cycle, where the discrimination of substrates and inhibitors occurs.


Author(s):  
Cinzia Dello Russo ◽  
Tiziano Bandiera ◽  
Monica Monici ◽  
Leonardo Surdo ◽  
Vincent Yip ◽  
...  

As human spaceflight continues with extended mission durations, the demand of effective and safe drugs is going to increase. To date, the medications used during missions (for space motion sickness, sleep disturbances, allergies, pain and sinus congestion) are administered under the assumption that they act similarly as on the Earth. During spaceflights however fluid shifts, muscle and bone loss, immune system dysregulation and changes in the gastrointestinal tract and metabolism are documented. These alterations may change the pharmacokinetics (PK) and pharmacodynamics. The information gained from bed-rest studies and from inflight observations is partial and demonstrates variability in drug PK. The objectives of this review are to report: i) the impact of the space environmental stressors on human physiology in relation to PK; ii) the state-of-the-art on experimental data in space and/or in ground-based models; iii) the validation of ground-based models for PK studies; and iv) the identification of possible research gaps.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4127
Author(s):  
Aline de Cristo Soares Alves ◽  
Franciele Aline Bruinsmann ◽  
Silvia Stanisçuaski Guterres ◽  
Adriana Raffin Pohlmann

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.


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