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Related Concept Videos

Dose-Response Relationship: Potency and Efficacy01:22

Dose-Response Relationship: Potency and Efficacy

The potency of a drug is the measure of its ability to produce a biological response and can be compared by looking at the half-maximum effective concentration or EC50 values of different drugs. A lower EC50 value indicates higher potency of the drug. In the dose–response curve of two antihypertensive drugs, candesartan and irbesartan, a significant difference is observed in their EC50 values. A lower EC50 value for candesartan indicates that it is more potent than irbesartan, as it produces...
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It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
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The empirical approach to drug therapy optimization relies on correlating pharmacological response with administered dosage. Such an approach can be costly, time-consuming, and often yields poor correlation due to variables like formulation factors and drug elimination characteristics. A more precise approach correlates response with plasma drug concentration or the amount of drug in the body, rather than dosage. This is achieved through pharmacokinetic-pharmacodynamic (PK/PD) modeling, which...
Dose-Response Relationship: Overview01:03

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Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
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Calculating drug dosage and accumulation in multiple-dose regimens is crucial for achieving therapeutic efficacy while avoiding toxicity. This involves determining the plasma drug concentrations over time to optimize dosing schedules. The principle of superposition is fundamental in this process, allowing for the prediction of drug concentration in plasma following multiple doses based on single-dose data.The principle of superposition asserts that the plasma concentration-time curves from...
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Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...

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hERG potency estimates based upon dose solution analysis: What have we learned?

Yusheng Qu1, Paul Schnier, Roger Zanon

  • 1Department of Toxicology Sciences, Amgen Inc., Thousand Oaks, CA 91320, USA. yqu@amgen.com

Journal of Pharmacological and Toxicological Methods
|September 6, 2011
PubMed
Summary
This summary is machine-generated.

Dose-solution analysis (DSA) confirmed nominal drug concentrations in most hERG channel assays. However, DSA did not improve potency estimates for poorly soluble or highly lipophilic and basic compounds.

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Area of Science:

  • Pharmacology
  • Drug Safety Assessment
  • Electrophysiology

Background:

  • The hERG channel is crucial for assessing drug-induced QTc interval prolongation risk.
  • Nominal drug concentration (NOM) is typically used for hERG assay potency calculations.
  • Dose-solution analysis (DSA) confirms actual drug concentrations (ACT) in vitro.

Purpose of the Study:

  • To evaluate if DSA improves the accuracy of hERG assay potency estimates.
  • To compare potency derived from ACT versus NOM concentrations.
  • To investigate factors influencing deviations between ACT and NOM values.

Main Methods:

  • Compared hERG IC50 values derived from NOM and ACT concentrations for 99 diverse agents.
  • Analyzed correlations between potency deviations and physicochemical properties (solubility, cLogP, pKa, molecular weight).

Main Results:

  • DSA confirmed NOM concentrations within 3-fold for 73.7% of agents.
  • 87.8% of agents showed IC50 ratios within 10-fold between NOM and ACT.
  • Compounds with >10-fold differences were less soluble, more lipophilic, and more basic.

Conclusions:

  • DSA generally confirmed nominal drug concentrations in hERG assays.
  • DSA did not significantly improve potency estimates for the majority of compounds.
  • For poorly soluble or highly lipophilic/basic compounds, DSA offered limited clarification.