Pharmacodynamics

Dissociation Constant Kd

TRDisosiyasyon Sabiti
Also known as:Equilibrium dissociation constant · KD

The equilibrium constant for dissociation of a drug–receptor complex, equal to the free drug concentration at which half of the receptors are occupied at equilibrium; a lower Kd means higher affinity.

Formula

Kd = [D] × [R] / [DR] = koff / kon Fractional occupancy = [D] / ([D] + Kd)

In depth

For reversible binding D + R ⇌ DR, Kd = [D][R]/[DR] at equilibrium, where [D], [R] and [DR] are the concentrations of free drug, free receptor and drug–receptor complex; it also equals koff/kon and is expressed in molar units (typically nM or μM). Fractional occupancy follows the Hill–Langmuir equation. Kd is measured by saturation radioligand binding, which also gives receptor density (Bmax), or by kinetic methods; its negative logarithm is pKd.

The equilibrium dissociation constant of a competing unlabelled inhibitor is termed Ki, and that of an antagonist determined functionally KB. Kd should not be confused with the acid dissociation constant (Ka, pKa) that governs ionisation.

Clinical pearl

Slow dissociation (long target residence time, 1/koff) prolongs receptor occupancy: tiotropium dissociates slowly from M3 receptors and is given once daily, whereas ipratropium dissociates faster and needs more frequent dosing.

Example drugs

Tiotropium Ipratropium
TRIn Turkish

Disosiyasyon Sabiti

İlaç–reseptör kompleksinin ayrışmasına ilişkin denge sabitidir; dengede reseptörlerin yarısının işgal edildiği serbest ilaç konsantrasyonuna eşittir ve düşük Kd yüksek afinite anlamına gelir.

Geri dönüşümlü D + R ⇌ DR bağlanmasında dengede Kd = [D][R]/[DR] olup [D], [R] ve [DR] sırasıyla serbest ilaç, serbest reseptör ve ilaç–reseptör kompleksi konsantrasyonlarıdır; Kd aynı zamanda koff/kon oranına eşittir ve molar birimlerle (genellikle nM veya μM) ifade edilir. Reseptör işgal oranı Hill–Langmuir denklemine uyar. Kd, reseptör yoğunluğunu (Bmax) da veren radyoligand doygunluk bağlanma deneyleriyle veya kinetik yöntemlerle ölçülür; negatif logaritması pKd'dir.

Yarışan işaretlenmemiş bir inhibitörün denge disosiyasyon sabitine Ki, işlevsel yöntemlerle belirlenen antagonist sabitine ise KB denir. Kd, iyonizasyonu belirleyen asit disosiyasyon sabitiyle (Ka, pKa) karıştırılmamalıdır.

Yavaş ayrışma (hedefte uzun kalış süresi, 1/koff) reseptör işgalini uzatır: tiotropiyum M3 reseptörlerinden yavaş ayrıştığı için günde bir kez kullanılırken, daha hızlı ayrışan ipratropiyum daha sık uygulama gerektirir.

Diğer adları:Denge disosiyasyon sabiti · Dissosiyasyon sabiti · Ayrışma sabiti
Updated 24.09.2026 1 views Educational reference — verify against current sources before clinical use.

Read next

AffinityAfinite

The strength of binding between a drug and its receptor or target, determined by the rates of association and dissociation and usually expressed as the equilibrium dissociation constant (Kd) or its negative logarithm (pKd).

 Inhibition Constantİnhibisyon Sabiti

The equilibrium dissociation constant of an inhibitor from its enzyme, receptor or transporter; an assay-independent measure of inhibitor affinity, with lower Ki values indicating more potent inhibition.

 ReceptorReseptör

A macromolecule, usually a protein, to which a drug or endogenous ligand binds specifically and thereby initiates a change in cell function that produces a biological response.

 LigandLigand

Any molecule, such as a drug, hormone or neurotransmitter, that binds to a specific site on a receptor or other macromolecule; binding alone does not imply activation or blockade.

 Half-Maximal Effective ConcentrationYarı Maksimal Etkili Konsantrasyon

The concentration of a drug that produces 50% of its own maximal effect (Emax); the standard measure of agonist potency in concentration–response studies.

 Spare ReceptorsYedek Reseptörler

Receptors in excess of those needed to produce a maximal response, so that a full agonist can elicit its maximal effect while occupying only a fraction of the available receptors.