28 papers · ranked by Valyu relevance
Jan Grzegorzewski, Janosch Brandhorst, Dimitra Eleftheriadou, Kathleen Green + 1 more
A multitude of pharmacokinetics studies have been published. However, due to the lack of an open database, pharmacokinetics data, as well as the corresponding meta-information, have been difficult to access. We present PK-DB (https://pk-db.com), an open database for pharmacokinetics information from clinical trials…
Rui-hong Yu, Yong-xiao Cao
On account of the disturbance from the distribution phase, the concentration-time curve of drugs cannot fully reflect the characteristics of elimination, and thus, it is difficult for present methods to obtain ideal pharmacokinetic parameters. This paper presents a method to determine pharmacokinetic parameters based…
Abad Khan, Lateef Ahmad, Faisal Raza, Saeed Ahmad Khan + 1 more
In drug discovery, pharmacokinetics (PK) and pharmacodynamics (PD) models are used for identification and selection of a drug candidate, and prediction of clinical response. These models can also facilitate characterizing the mechanism of action and disease behaviour of a given drug aiding in assessing efficacy and…
Authors not listed
Accurate modeling of drug concentration--time (C--t) profiles is central to pharmacokinetics (PK) and plays a critical role in both early-stage compound selection and late-stage individualized dosing. Traditional PK model offer mechanistic interpretability but often rely on rigid assumptions, extensive…
Saganuwan Alhaji Saganuwan
Background Pharmacokinetics (PK) is the process of absorption, distribution, metabolism and elimination (ADME) of drugs. Some drugs undergo zero-order kinetics (ethyl alcohol), first order kinetics (piroxicam) and mixed order kinetics (ascorbic acid). Drugs that undergo Michaelis-Menten metabolism are characterized by…
Klara Valko
Background and purpose The steady-state volume of distribution reflects the extent to which drugs partition between plasma and tissues and is closely related to the tissue-to-plasma partition coefficient. In pharmacokinetics, different modelling frameworks have led to ongoing debate regarding the role of plasma protein…
Ellen Niederberger, Michael J. Parnham, Elmira Arab-Tehrany
It is well known that lifestyle changes can alter several physiological functions in the human body. For exercise and diet, these effects are used sensibly in basic therapies, as in cardiovascular diseases. However, the physiological changes induced by exercise and a modified diet also have the capacity to influence…
Françoise Van Bambeke, Sebastian Wicha, Paul M. Tulkens, Markus Zeitlinger
'Markus Zeitlinger'] Pharmacokinetics (PK) is the discipline investigating the absorption, distribution, metabolization and elimination of a drug in the body. This term was first introduced in 1953 by Prof Hartmut Dost, a pediatrician and active member of the German Pharmacological Society, who was concerned with the…
Koichi Handa, Saki Yoshimura, Michiharu Kageyama, Takeshi Iijima
AI is expected to help identify excellent candidates in drug discovery. However, we face a lack of data as it is time consuming and expensive to acquire raw data perfectly for many compounds. Hence, we tried to develop a novel QSAR method to predict a parameter more precisely from an incomplete dataset via optimizing…
Pantelis Sopasakis, Haralambos Sarimveis, Panos Macheras, Aristides Dokoumetzidis
'Aristides Dokoumetzidis'] Abstract We are witnessing the birth of a new variety of pharmacokinetics where non-integer-order differential equations are employed to study the time course of drugs in the body: this is dubbed "fractional pharmacokinetics". The presence of fractional kinetics has important clinical…
S. Piekarski, M. Rewekant
In 2011 it has been suggested that inconsistencies in pharmacokinetics should be eliminated after deriving "pharmacokinetic parameters" from conservation laws [3]. In the following text a simple system of conservation laws for extra - vascular administration of a drug is explicitly given and preliminary discussion…
S. Piekarski, M. Rewekant
In the text S.Piekarski, M.Rewekant, "On applications of conservation laws in pharmacokinetics",(arXiv:1208.3847) it has been mentioned that some information on bioavailability and bioequivalence of drugs can be obtained from simulations based on the conservation laws. Here we shortly discuss that possibility starting…
Jan Grzegorzewski, Florian Bartsch, Adrian Köller, Matthias König
Caffeine is by far the most ubiquitous psychostimulant worldwide found in tea, coffee, cocoa, energy drinks, and many other beverages and food. Caffeine is almost exclusively metabolized in the liver by the cytochrome P-450 enzyme system to the main product paraxanthine and the additional products theobromine and…
Urban Fagerholm, Sven Hellberg, Jonathan Alvarsson, Ola Spjuth
The ANDROMEDA software, based on machine learning, conformal prediction and a new physiologically-based pharmacokinetic model, was used to predict and characterize the human clinical pharmacokinetics of 30 selected modern small antibiotic compounds (investigational and marketed drugs). A majority of clinical…
Nazanin Ahmadi Daryakenari, Shupeng Wang, George Em Karniadakis
In the field of pharmacokinetics and pharmacodynamics (PKPD) modeling, which plays a pivotal role in the drug development process, traditional models frequently encounter difficulties in fully encapsulating the complexities of drug absorption, distribution, and their impact on targets. Although multi-compartment models…
Elias Toulitsis, Athanasios A. Tsekouras, Panos Macheras, Elżbieta Wyska
'Elżbieta Wyska'] Background: It has been demonstrated that the concept of infinite absorption time, associated with the absorption rate constant, which drives a drug’s gastrointestinal absorption rate, is not physiologically sound. The recent analysis of oral drug absorption data based on the finite absorption time…
Hongtao Zhao
Plasma protein is crucial for understanding pharmacokinetics, pharmacodynamics, and safety, yet it is often not recommended as a primary parameter for optimization in drug design. This study challenges this view by revisiting established pharmacokinetic models to elucidate a bidirectional strategy for…
Authors not listed
Integrated understanding of pharmacokinetics (PK) and pharmacodynamics (PD) is a key aspect of successful drug discovery. Yet in generative computational drug design, the focus often lies on optimizing potency. Here we integrate PK property predictions in DrugEx, a generative drug design framework and we explore the…
Fabio Broccatelli, Radha Ramakrishnan
Physiologically based pharmacokinetics (PBPK) modeling is a valuable tool in drug development and candidate selection. However, its widespread adoption in early stages of drug discovery remains limited. This study proposes a novel simplified approach to estimate organ-to-plasma ratio (K_p_) values based on measured or…
S. Piekarski, M. Rewekant
Simple example of balance equations for the intravenous administration of drug has been given in 2011 and the corresponding equations for extravasal administration are in the text. In principle, the equations of that kind allow one to describe in the self – consistent manner different processes of administration…
Hirokazu Wakuda, Yue Xiang, Jasleen K. Sodhi, Naoto Uemura + 1 more
It is generally believed that bioavailability ( $F$) calculated based on systemic concentration area under the curve (AUC) measurements cannot exceed 1.0, yet some published studies report this inconsistency. We teach and believe, based on differential equation derivations, that rate of absorption has no influence on…
Beatrice Stemmer Mallol, Jan Grzegorzewski, Hans-Michael Tautenhahn, Matthias König
Talinolol is a cardioselective beta-blocker that was previously used to treat heart failure and myocardial infarction. Following the development of new, more effective beta-blockers with better study results, talinolol is now only used clinically for the treatment of arterial hypertension. In basic science, talinolol…
Koichi Handa, Daichi Fujita, Mariko Hirano, Saki Yoshimura + 2 more
Given the aging populations in advanced countries globally, many pharmaceutical companies have focused on developing central nervous system (CNS) drugs. However, due to the blood-brain barrier, drugs do not easily reach the target area in the brain. Although conventional screening methods for drug discovery involve the…
Lingfei Huang, Yixi Liu, Zheng Jiao, Junyan Wang + 2 more
'Jianhua Mao'] Data were obtained from 71 pediatric patients with PNS, along with 525 TAC trough concentrations at steady state. The demographic, medical, and treatment details were collected. Genetic polymorphisms of CYP3A41G, CYP3A53, and ABCB1-C3435T were analyzed. The PPK models were developed using nonlinear…
Devendra Dhaked, Marc Nicklaus
This mini-review reports on effects that tautomerism has on predicted and clinically observed small-molecule properties important for drug design and drug behaviour in the patient. We present examples of both pharmacokinetics and pharmacodynamics effects. The importance of tautomerism on drugs’ formulation and possible…
Xiaojun Cai, Wang Zheng-xin, Li Ruidong, Yifeng Tao + 7 more
'Zhang Xiaofei' 'Juan Li' 'Conghuan Shen' 'Xiaoyan Qiu' 'Jianhua Li' 'Zheng Jiao'] Diverse tacrolimus population pharmacokinetic (popPK) models in adult liver transplant recipients have been established to describe the PK characteristics of tacrolimus in the last two decades. However, their extrapolated predictive…
Authors not listed
Therapeutic drug monitoring enables personalized cancer medicine by dosing patients with chemotherapy based on the patient’s own unique rate of drug clearance and metabolic degradation. These rates significantly influence the plasma concentration which influences patient outcomes. This is especially true for the…
Yue Huang, Hui Yin Tan, Jiaqi Yuan, Ruipeng Mu + 8 more
What happens to macromolecules in vivo? What drives structure-activity relationship and in vivo stability for antibody-drug conjugates (ADCs)? These interrelated questions are increasingly relevant due to the re-emerging importance of ADCs as an impactful therapeutic modality and the gaps that exist in our…