AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesDisciplines and OccupationsTechnology, Industry, AgricultureNamed GroupsHealth Care
Half-LifeArea Under CurvePharmacokineticsMetabolic Clearance RateBiological AvailabilityAdministration, OralInjections, IntravenousDrug InteractionsInfusions, IntravenousTissue DistributionCross-Over StudiesChromatography, High Pressure LiquidDose-Response Relationship, DrugFood-Drug InteractionsDrug Administration ScheduleBiotransformationCytochrome P-450 CYP3AProdrugsModels, BiologicalNeoplasmsInfusions, ParenteralRitonavirKineticsAnti-Bacterial AgentsDouble-Blind MethodInjections, IntramuscularAntineoplastic AgentsDrug Dosage CalculationsAntifungal AgentsMaximum Tolerated DoseCapsulesDelayed-Action PreparationsAnti-Infective AgentsDrug CombinationsKetoconazoleTherapeutic EquivalencyTriazolesCephalosporinsDrug Therapy, CombinationStereoisomerismAbsorptionMidazolamAnti-HIV AgentsTime FactorsTabletsInjections, SubcutaneousHIV Protease InhibitorsHealthy VolunteersMacaca fascicularisDrug MonitoringQuinolinesP-GlycoproteinPyrimidinonesPlasmaPopulationRats, Sprague-DawleyAryl Hydrocarbon HydroxylasesAntineoplastic Agents, PhytogenicDogsChromatography, LiquidBlisterBlood ProteinsTreatment OutcomeCytochrome P-450 CYP2D6Herb-Drug InteractionsChemistry, PharmaceuticalFleroxacinSuspensionsBileIntestinal AbsorptionTandem Mass SpectrometryFluoroquinolonesAdministration, IntravenousGlucuronidesDrug EvaluationPharmacogeneticsAlfentanilLopinavirAdministration, RectalCitrus paradisiPyridinesCytochrome P-450 Enzyme SystemGentamicinsDigoxinDrug CarriersRifampinProbenecidNonlinear DynamicsAntibodies, MonoclonalCilastatinCefotaximeQuinolonesBenzoxazinesAnticonvulsantsSulfonamidesCiprofloxacinPharmaceutical PreparationsPharmaceutical VehiclesDrug Administration RoutesDrug Evaluation, Preclinical
PharmacodynamicsMetabolismVivoPBPKBioavailabilityAbsorptionTissue DistributionPhysiologically based pharmacokineticDosesCerebrospinal fluidHumansTolerabilityEfficacyPharmacologyDrugKineticsMolecularCharacterizeStudyFormulationRatsCompoundsMathematical modelsDescribeAdministrationPracticeConcentrationsComputationalDistributionConventionalPredictionXenograft modelMethodsVitroApproachCellularCompartmentalTumor cellsEvaluate
Pharmacodynamics6
  • The pharmacology of estradiol, an estrogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration. (wikipedia.org)
  • Pharmacokinetics-pharmacodynamics of tazobactam in combination with piperacillin in an in vitro infection model. (jmilabs.com)
  • Effects of disease states on pharmacokinetics and pharmacodynamics of drugs. (nottingham.ac.uk)
  • Pharmacokinetics and pharmacodynamics of chlorpyrifos and 3,5,6-trichloro-2-pyridinol in rat saliva after chlorpyrifos administration. (cdc.gov)
  • The objective of this study was to quantitatively evaluate in vivo pharmacokinetics and pharmacodynamics of CPF and TCPy in saliva after CPF administration. (cdc.gov)
  • Developmental changes in pharmacokinetics and pharmacodynamics. (msdmanuals.com)
Metabolism5
  • We applied physiologically based pharmacokinetic (PBPK) modeling to study the dose-dependent metabolism and excretion of verapamil and its preformed metabolite, norverapamil, to unravel the kinetics of norverapamil formation via N -demethylation. (aspetjournals.org)
  • Pharmacokinetics (PK) can aid in understanding information and in predicting outcomes with respect to the absorption, disposition, metabolism, and excretion of chemicals. (nationalacademies.org)
  • The pharmaceutical literature consists of numerous examples of 2-D QSARs, 3-D QSARs and expert systems for modelling the individual components or phases of drug disposition and pharmacokinetics (i.e. absorption, distribution, metabolism and *Corresponding author. (cdc.gov)
  • Several reviews and reports present the advantages and limitations of the currently available algorithms and software for in silico modelling of the drug dissolution/bioavailability, oral absorption rate/fraction, volume of distribution, path- ways, affinities or rates of metabolism, renal excretion rate as well as affinity for specific transporters [3-20]. (cdc.gov)
  • Metabolism and elimination Pharmacokinetics refers to the processes of drug absorption, distribution, metabolism, and elimination. (msdmanuals.com)
Vivo5
  • In addition, when translating in vitro cytotoxicity data to predict in vivo active clinical dose for blinatumomab, the choice of model leads to a notable difference in dose prediction. (springer.com)
  • The dose predicted by the 2D model aligns better with the approved clinical dose and the prediction is robust under variations in the in vitro to in vivo translation assumptions. (springer.com)
  • Recent reports have identified a redox-silent analogue of VE, α -tocopheryl succinate ( α -TOS), as a potent anticancer agent with a unique structure and pharmacokinetics in vivo . (nature.com)
  • Mouse models of cancer have consistently been used to determine the in vivo activity of new anti-cancer therapeutics prior to clinical development and testing in humans. (atdrik.com)
  • It was designed using computational modeling based on a naturally occurring indole-3-carbinol and its in vivo condensation products. (sri.com)
PBPK19
  • Li L, Gardner I, Gill K. Modeling the binding kinetics of bispecific antibodies under the framework of a minimal human PBPK model. (springer.com)
  • Enantiomeric disposition and auto-inhibition of verapamil failed to perturb these estimaties according to PBPK modeling, due to the low values of the Michaelis-Menten constant, K m , and inhibition parameter, k I . (aspetjournals.org)
  • When developing human PBPK models, the insight gained from prior animal PBPK models based on nonclinical data informed the optimization of the lipophilicity input of the compounds and the selection of the appropriate mechanistic tissue partition methods. (aspetjournals.org)
  • The accuracy of V 1 , V ss , and V β values predicted that using human PBPK models developed in accordance with prior animal PBPK models was superior to using those predicted using conventional approaches, such as allometric scaling, especially for V 1 and V β . (aspetjournals.org)
  • PBPK models predicted V 1 , V ss , and V β values for almost all compounds within 3-fold errors, resulting in better predictions of plasma concentration profiles than allometric scaling. (aspetjournals.org)
  • The distribution volumes predicted using human PBPK models based on prior animal PBPK modeling were more accurate than those predicted without reference to animal models. (aspetjournals.org)
  • This study demonstrated that human PBPK models developed with consideration of animal PBPK models could accurately predict distribution volumes in various elimination phases. (aspetjournals.org)
  • These models, which are based on the anatomy and physiology of mammals and use the vast amount of published comparative physiologic data, are known as physiologically based pharmacokinetic (PBPK) models. (nationalacademies.org)
  • however, PBPK models clearly reveal what data they require and thus what experiments will be needed to make them useful. (nationalacademies.org)
  • If the dynamic processes modeled by the PBPK approach are all directly proportional to administered concentrations, then the extrapolation can be relatively straightforward. (nationalacademies.org)
  • PBPK models are useful, because they permit estimation of peak concentrations. (nationalacademies.org)
  • In this work, we quantitatively predicted the DDI between oxycodone and diazepam through empirical PK modeling, minimal physiologically-based PK (PBPK) modeling and full PBPK modeling. (pitt.edu)
  • Physiologically-based pharmacokinetic (PBPK) models are increasingly finding use in risk assessment applications of data-rich compounds. (cdc.gov)
  • In this regard, SARs, QSARs and QPPRs are potentially useful for computing the chemical-specific input parameters of PBPK models. (cdc.gov)
  • Based on the frequency of occurrence of molecular fragments (CH3, CH2, CH, C, C¼C, H, benzene ring and H in benzene ring structure) and exposure conditions, the available QSAR-PBPK models facilitate the simulation of tissue and blood concentrations for some inhaled volatile organic chemicals. (cdc.gov)
  • The application domain of existing QSARs for developing PBPK models is limited, due to lack of relevant data for diverse chemicals and mechanisms. (cdc.gov)
  • Even though this approach is conceptually applicable to non-volatile and high molecular weight organics as well, it is more challenging to predict the other PBPK model parameters required for modelling the kinetics of these chemicals (particularly tissue diffusion coefficients, association constants for binding and oral absorption rates). (cdc.gov)
  • Physiologically-based pharmacokinetic (PBPK) modelling refers to the development and evaluation of mathematical descriptions of the ADME of chemicals in biota based on proven/hypothetical mechanistic determinants [21]. (cdc.gov)
  • PBPK models essentially represent a systems biology approach to the study of ADME and are increasingly finding use in screening-level as well as quantitative risk assessments to reduce the uncertainties associated with interspecies, route-to-route, and high-dose to low-dose extrapolations of tissue dose of chemicals [21-24]. (cdc.gov)
Bioavailability2
  • The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of multiple ascending oral doses of AZD1236 given to healthy young subjects for 13 days and to evaluate the single-dose relative bioavailability of the oral suspension and oral tablet formulations. (astrazenecaclinicaltrials.com)
  • The pharmacokinetics of PS916-FTC was characterized by low bioavailability (8.40%) after oral administration . (bvsalud.org)
Absorption1
Tissue Distribution1
Physiologically based pharmacokinetic1
  • A physiologically based pharmacokinetic and pharmacodynamic model for CPF was modified and predicted the data reasonably well. (cdc.gov)
Doses3
  • Pharmacokinetics inform the estimation of potential therapeutic doses and safety margins before first-in-human studies. (aspetjournals.org)
  • This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults. (researchgate.net)
  • The pharmacokinetics of psilocin were linear within the twofold range of doses, and the elimination half-life of psilocin was 3 h (standard deviation 1.1). (researchgate.net)
Cerebrospinal fluid1
Humans2
  • Predicting the pharmacokinetics of compounds in humans is an important part of the drug development process. (aspetjournals.org)
  • In this study, the plasma concentration profiles of 10 marketed compounds exhibiting two-phase elimination after intravenous administration in humans were evaluated in terms of distribution volumes just after intravenous administration ( V 1 ), at steady state ( V ss ), and in the elimination phase ( V β ) using physiologically based pharmacokinetic (PBPK) modeling implemented in a commercially available simulator (Simcyp). (aspetjournals.org)
Tolerability1
  • The overall objective of this open-label, nonrandomized, 2-part Phase 1a/1b study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) and to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of oral TACH101 in participants with advanced and metastatic solid tumors. (clinicaltrials.gov)
Efficacy2
  • The selected BF-30 derivative was further subjected to the preclinical efficacy study and chronic evaluation of anti-tumour effects melanoma-bearing model mice. (jcancer.org)
  • The contribution of pharmacogenetics (PG) will be evaluated in a large population subset from a phase III clinical trial with respect to patient efficacy and safety outcomes by incorporating PG data into population pharmacokinetic (PK) models for six major TB drugs and risk algorithms for unfavorable treatment outcomes and to develop and evaluate PG-based dosing algorithms for novel high-dose rifapentine-based regimens. (cdc.gov)
Pharmacology1
Drug6
  • Schropp J, Khot A, Shah DK, Koch G (2019) Target-mediated drug disposition model for bispecific antibodies: properties, approximation, and optimal dosing strategy. (springer.com)
  • The main assumption of allometric scaling is that the factors governing the pharmacokinetics of a drug should scale in relation to body size ( Boxenbaum, 1982 ). (aspetjournals.org)
  • The purpose of this study was to develop a general approach for comparing both models using a stochastic model of intra- and extravascular drug distribution. (nih.gov)
  • We have significant collaboration between researchers involved with pharmacokinetics and drug disposition and those in nanomaterials formulation, nucleic acid therapeutics and RNA biology, allergy and infection. (nottingham.ac.uk)
  • The plasma drug concentration-time profile was characteristic of a two-compartment open model. (tubitak.gov.tr)
  • Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. (bvsalud.org)
Kinetics2
  • The relative dispersion of cellular residence times is introduced as a model-independent measure of cytoplasmic equilibration kinetics, which indicates whether diffusion through the cytoplasm is rate limiting. (nih.gov)
  • If differences in outflow curve shapes (their relative skewness) cannot be detected, independent information on binding and/or diffusion kinetics is necessary to avoid model misspecification. (nih.gov)
Molecular4
  • In PD study, we used molecular modeling techniques including molecular docking, molecular dynamics simulations and MM/PBSA calculations to predict the pharmacodynamic interaction between opioids and benzodiazepines. (pitt.edu)
  • Investigations are performed using a variety of chemical, biochemical and molecular approaches with isolated enzyme, cell culture and animal model systems. (cdc.gov)
  • Diseño molecular de fármacos con propósitos específicos (unión al ADN, inhibición enzimática, eficacia contra el cáncer, etc.) basado en el conocimiento de propiedades moleculares tales como la actividad de los grupos funcionales, la geometría molecular y la estructura electrónica, así como en la información catalogada sobre fármacos análogos. (bvsalud.org)
  • El diseño de fármacos generalmente consiste en el modelado molecular asistido por ordenador y no comprende la FARMACOCINÉTICA, el análisis de las dosis ni el análisis de la administración del fármaco. (bvsalud.org)
Characterize1
  • Jiang X, Chen X, Carpenter TJ, Wang J, Zhou R, Davis HM et al (2018) Development of a Target cell-Biologics-Effector cell (TBE) complex-based cell killing model to characterize target cell depletion by T cell redirecting bispecific agents. (springer.com)
Study2
  • The present study was designed to investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (atorvastatin, pravastatin, simvastatin) on the pharmacokinetics of losartan and its active metabolite EXP-3174 in rats. (karger.com)
  • Leveraging existing technology and stored specimens, HLA genes and variants of immune response genes (IL-10, TNFA, IL1A, IL12B, and CD80) are to be sequenced and genotyped, respectively, establishing a broader set of Hemophilia Inhibitor Research Study (HIRS) enrollees to evaluate existing inhibitor risk prediction models and to investigate the feasibility of developing better models using curated variants in a diverse patient population. (cdc.gov)
Formulation1
Rats4
  • We have investigated the pharmacokinetics of SNF472 administration in rats and its inhibitory effects on CVC. (uantwerpen.be)
  • SNF472 was studied in three rat models: (1) prevention of vitamin D3-induced CVC with an intravenous SNF472 bolus of 1 mg/kg SNF472, (2) inhibition of progression of vitamin D3-induced CVC with a subcutaneous SNF472 bolus of 10 or 60 mg/kg SNF472, starting after calcification induction, (3) CVC in adenine-induced uremic rats treated with 50 mg/kg SNF472 via i.v. 4h -infusion. (uantwerpen.be)
  • The pharmacokinetics and bio-disposition of PS916-FTC were studied in rats after oral or intravenous administration . (bvsalud.org)
  • These findings supported the understanding of pharmacokinetics and bio-disposition of PS916 in rats and provide relevant information for future design of clinical studies. (bvsalud.org)
Compounds2
  • More recently, compartmental models based on chemical transfer in and out of body organs, or even portions of organs, have been developed to describe and predict relationships between administered dose and biologically effective concentrations of parent compounds or metabolites in critical target tissues. (nationalacademies.org)
  • It is envisioned that a combination of biomonitoring compounds like TCPy in saliva coupled with computational modeling will form an approach to measure pesticide exposure to susceptible human populations such as agricultural workers. (cdc.gov)
Mathematical models2
  • Traditionally, analysis has been done empirically, with direct use of the data at hand, and possibly with the aid of simple mathematical models that use overall mass balances. (nationalacademies.org)
  • Pharmacometric models are mathematical models aiming to describe the relationship between pharmaceutical therapy and patient response. (lu.se)
Describe3
  • Here, we present a next-generation two-step binding mathematical model for TCEs to describe trimer formation. (springer.com)
  • In conclusion, the 2D model with trans-avidity to describe trimer formation is an improved approach for TCEs and is likely to produce more accurate predictions to support TCE development. (springer.com)
  • An inhibitory sigmoidal E max model was used to describe the effect of SNP. (frontiersin.org)
Administration3
  • After IV administration, plasma concentrations of flumazenil follow a two-exponential decay model. (nih.gov)
  • The pharmacokinetics of cefepime was studied in 5 goats following i.v. and i.m. administration of 10 mg/kg of body weight. (tubitak.gov.tr)
  • Following i.v. administration, the cefepime plasma concentration-time curves were best fitted in a one-compartment open model. (tubitak.gov.tr)
Practice1
  • model-based dosing guidance agrees with current practice. (frontiersin.org)
Concentrations1
  • The plasma concentrations of idarubicin are best described by a two or three compartment open model. (nih.gov)
Computational1
  • Computational models supporting TCE development must predict trimer formation accurately. (springer.com)
Distribution2
  • Distribution between well-stirred compartments is the classical paradigm in pharmacokinetics. (nih.gov)
  • Criteria for model discrimination are developed using the first three central moments (mean, variance, and skewness) of the cellular residence time and organ transit time distribution, respectively. (nih.gov)
Conventional1
Prediction3
  • Enhancing the evaluation of genetic risk prediction models for inhibitor development among people with hemophilia in different populations. (cdc.gov)
  • A central aspect of pharmacometric models is prediction of individual responses to therapy based on covariates (i.e. patient characteristics). (lu.se)
  • The covariates have historically been limited to patient demographics such as weight, height and sex and the covariate modelling has focused on which covariates that are relevant for prediction of response. (lu.se)
Xenograft model1
  • The most widely used one is the human tumor xenograft model. (atdrik.com)
Methods1
Vitro1
  • Compared to the 3D binding model where the reactants are described in terms of concentration, the 2D model predicts less sensitivity of trimer formation to varying cell densities, which better matches changes in EC 50 from in vitro cytotoxicity assay data with varying E:T ratios. (springer.com)
Approach1
  • Also in capillary-issue exchange modeling a barrier-limited approach is mostly adopted. (nih.gov)
Cellular2
  • After matching the models for the relative dispersion the remaining differences in relative skewness are predicted, discussing the relative roles of membrane permeability, cellular binding and cytoplasmic transport. (nih.gov)
  • It provides a general framework for the modeling of cellular pharmacokinetics. (nih.gov)
Compartmental1
Tumor cells1
  • In this model, human tumor cells (patient derived tumors (PDX) or tumor cell lines) are transplanted, either under the skin (xenograft) or directly into the organ (orthotopic) in which the tumor originated or associated, into immunocompromised (nude or SCID) mice that do not reject human cells. (atdrik.com)
Evaluate1
  • To evaluate anti-tumour effects and mechanism of novel BF-30 derivative via cell-based assays and melanoma-bearing model mice. (jcancer.org)