ED50

Article Author:
Brian Kenny
Article Editor:
Arthur McPhee
Updated:
2/6/2019 7:44:44 PM
PubMed Link:
ED50

Definition/Introduction

The ED50 (median effective dose) is the dose of a medication that produces a specific effect in 50% of the population that takes that dose). This number has common use as what a clinician or patient can expect for a drug effect, but clinicians may use a different dosage for their particular intended effect, depending on the balance of need or benefit of the drug versus the toxicity of the drug. The toxic dose in 50% of the population is called TD50; the ED50 should hopefully be much less than the TD50, as this would indicate an effective medication at a lower dose.[1]

The ED50 for a particular medication derives from a dose-response curve, in which the ED50 is at the dosage (x-axis) where there is 50% of the desired response (y-axis).

The ED50 should be used as a clinical starting point for practitioners when prescribing medications, as adjustments are made to balance efficacy and toxicity. The E-max would be equivalent to the maximum effect the drug may have. It is important to remember that as dosages increase, toxicities will increase, and they may not be directly proportionate. Each patient requires individualized goals of treatment and should be monitored for such to ensure the lowest dose possible, especially for long term treatment.

There are two forms of dose-response curves, graded and quantal. Graded answers the question, ‘how much’; whereas, quanta answers, ‘yes or no.’ The ED50 may change depending on the question the clinician is trying to answer, therefore, using the recommended ED50 as a starting point is recommended and making adjustments based on the clinical outcomes for the patient.

Issues of Concern

Research shows that even when manufacturers set dose estimation guidelines, it seems to have little impact on what dose clinicians prescribe. Another overlooked aspect of the ED50, of which clinicians and pharmacists may be unaware, is the patient by patient variation in the ED50 depending on their weight, height, fat content, pharmacokinetics, and pharmacodynamics.[1]

ED50 for medications and the recommended dosages based from studies derive for surrogate endpoints (ex: blood pressure after taking medication) rather than the long-term effects the drug has on the body.[2][1]

Studies have shown that regarding the ED50, many deem mortality to be too small of an endpoint and uncommon to be of particular interest for a medication. However, on a grand scheme in a large population, medications that may have substantial clinical benefits may also lead to severe consequences and death. An example of this is digoxin, which has had efficacy in heart failure and atrial fibrillation, but at commonly used dosages caused a net increase in mortality.[1]

Clinical Significance

When dosing drugs for significant periods, the dosage for the desired effect must be monitored to ensure that the patient does not approach the toxic dose.[3]

In a recent study, researchers found that prescription medications have contributed to over 10% of hospital admission and over 15% of hospital mortality.[4] This is not to say that all of these cases are from higher dosages than were needed for the intended efficacy, but a persistently high dose needs to be re-evaluated regularly to ensure problem exposure to the medication is occurring.

Research has found that lower dosages of medications such as aspirin and statins, when used at dosages near their ED50 are the most efficacious from a preventative standpoint. For example, an 81 mg dosage of Aspirin after a first clinical heart event is just as effective as dosages of over 100mg.[5] 

It is important to remember the different clinical endpoints in patients as well, and as patients change in weight, age, etc. their ED50 may also be altered. Clinicians are prone to work towards specific metrics, such as a hemoglobin A1C of 6% for a diabetic patient or a blood pressure of 120/80mmHg. However, these are clinical guidelines and should act as a starting point towards which the clinician believes their patient should work. If clinicians are not mindful of these considerations, patients may receive doses of medications that are toxic to them which may be a standard dosage for another patient.[1]


References

[1] Dimmitt S,Stampfer H,Martin JH, When less is more - efficacy with less toxicity at the ED50. British journal of clinical pharmacology. 2017 Jul;     [PubMed PMID: 28387051]
[2] Martin JH,Fay MF, Surrogate end-points in clinical practice: are we providing worse care? Internal medicine journal. 2010 Jun;     [PubMed PMID: 20636827]
[3] Konstam MA,Neaton JD,Dickstein K,Drexler H,Komajda M,Martinez FA,Riegger GA,Malbecq W,Smith RD,Guptha S,Poole-Wilson PA, Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet (London, England). 2009 Nov 28;     [PubMed PMID: 19922995]
[4] Mouton JP,Mehta U,Parrish AG,Wilson DP,Stewart A,Njuguna CW,Kramer N,Maartens G,Blockman M,Cohen K, Mortality from adverse drug reactions in adult medical inpatients at four hospitals in South Africa: a cross-sectional survey. British journal of clinical pharmacology. 2015 Oct;     [PubMed PMID: 25475751]
[5] Campbell CL,Smyth S,Montalescot G,Steinhubl SR, Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA. 2007 May 9;     [PubMed PMID: 17488967]