Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and…
Pharmacology
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Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the cellular levels of the second messengers, cAMP and cGMP, by controlling their rates of degradation. There are 11 different PDE families, with each family typically having…
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The present paper proposes a modeling and simulation strategy for the prediction of pharmacokinetics (PK) of drug candidates by using currently available in silico and in vitro based prediction tools for absorption, distribution, metabolism and…
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CAMP is a second messenger that is essential for relaying hormonal responses in many biological processes. The discovery of the cAMP target Epac explained various effects of cAMP that could not be attributed to the established targets PKA and cyclic…
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The objective of this study was to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelium-derived relaxing factor (EDRF). EDRF is an unstable humoral substance released from artery and…
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Data obtained from 318 adult patients treated under the linezolid compassionate-use protocol were used to develop a population model of the pharmacokinetics of intravenous and oral linezolid. All of the patients received 600 mg of linezolid every 12…
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Two 14-day, placebo-controlled, double-blind studies evaluated the fasting pharmacokinetics, safety, and tolerability of aripiprazole, a new antipsychotic, in healthy male subjects. In Study 1, 37 subjects were randomized to aripiprazole 5 mg, 10…
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The application of physiologically-based pharmacokinetic (PBPK) modeling is coming of age in drug development and regulation, reflecting significant advances over the past 10 years in the predictability of key pharmacokinetic (PK) parameters from…
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Growth and development can be investigated using readily observable demographic factors such as weight and age. Size is the primary covariate and can be referenced to a 70-kg person with allometry using a coefficient of 0.75 for clearance and 1 for…
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The perceived failure of new drug development has been blamed on deficiencies in in vivo studies of drug efficacy and safety. Prior simulation of the potential exposure of different individuals to a given dose might help to improve the design of…
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The beta1- and beta2-adrenergic receptors (betaARs) on the surface of cardiomyocytes mediate distinct effects on cardiac function and the development of heart failure by regulating production of the second messenger cyclic adenosine monophosphate…
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Recent advancements in Information and Communication Technologies (ICT) have resulted in staggering growth in the development of e-technologies that have fundamentally transformed the technological, economical and social landscapes. Whats more, the…
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Model-based drug development (MBDD) has been recognized as a concept to improve the efficiency of drug development. The acceptance of MBDD from regulatory agencies, industry, and academia has been growing, yet todays drug development practice is…
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PURPOSE: To compare the performance of the standard lag time model (LAG model) with the performance of an analytical solution of the transit compartment model (TRANSIT model) in the evaluation of four pharmacokinetic studies with four different…
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Nuclear receptors are major targets for drug discovery and have key roles in development and homeostasis, as well as in many diseases such as obesity, diabetes and cancer. This review provides a general overview of the mechanism of action of nuclear…
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During the course of chemotherapy, certain drugs are predominant in their bactericidal activities. Isoniazid is responsible for an initial kill of about 95% of organisms during the first 2 days of treatment. Its bactericidal role is then replaced by…
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(i) To describe an example of the development work required for building a 'pediatric physiologically based pharmacokinetic' (P-PBPK) model (Simcyp Pediatric ADME Simulator), (ii) to replicate pediatric clinical studies and undertake theoretical…
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Ph.D. StudentSchool of Pharmacy, Department of Pharmacology -
Ph.D. StudentClinical Pharmacology and Pharmacoepidemiology, University of Heidelberg -
ProfessorUniversity of São Paulo -
Student (Master)Kingston, Canada -
LecturerBandung, Indonesia