Pharmacodynamics

Inhibition Constant Ki

TRİnhibisyon Sabiti
Also known as:Inhibitor constant · Inhibitor dissociation constant

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.

Formula

Ki = IC50 / (1 + [S] / Km) AUCi / AUC ≈ 1 + [I]u / Ki

In depth

Ki is derived from inhibition experiments by correcting for substrate or radioligand concentration, most often by converting IC50 with the Cheng–Prusoff equation ([S], substrate concentration; Km, Michaelis constant), or from kinetic analyses that also reveal the mode of inhibition: competitive, non-competitive, uncompetitive or mixed. For mechanism-based (time-dependent) inhibitors, KI and kinact are used instead.

In interaction assessment, comparing the unbound inhibitor concentration [I]u with Ki estimates the likely rise in victim-drug exposure; in the simplest static model for reversible inhibition of a pathway that fully eliminates the victim drug, the AUC ratio with and without inhibitor (AUCi/AUC) ≈ 1 + [I]u/Ki.

Clinical pearl

Inhibitors whose unbound concentrations greatly exceed their Ki for a pathway, such as ketoconazole or itraconazole for CYP3A4, can markedly increase exposure to sensitive substrates such as simvastatin.

Example drugs

Ketoconazole Itraconazole
TRIn Turkish

İnhibisyon Sabiti

Bir inhibitörün enzim, reseptör veya taşıyıcıdan ayrışmasına ait denge disosiyasyon sabitidir; deney koşullarından bağımsız bir inhibitör afinitesi ölçüsüdür ve düşük Ki değeri daha güçlü inhibisyonu gösterir.

Ki, inhibisyon deneylerinden substrat veya radyoligand konsantrasyonu hesaba katılarak türetilir; bu çoğunlukla IC50 değerinin Cheng–Prusoff denklemiyle ([S]: substrat konsantrasyonu; Km: Michaelis sabiti) dönüştürülmesiyle ya da inhibisyon tipini (kompetitif, nonkompetitif, unkompetitif veya karışık) da ortaya koyan kinetik analizlerle yapılır. Mekanizma temelli (zamana bağımlı) inhibitörlerde bunun yerine KI ve kinact kullanılır.

Etkileşim değerlendirmesinde bağlanmamış inhibitör konsantrasyonunun ([I]u) Ki ile karşılaştırılması, etkilenen ilacın maruziyetindeki olası artışı öngörmeye yarar; etkilenen ilacı tamamen elimine eden bir yolağın geri dönüşümlü inhibisyonuna ilişkin en basit statik modelde inhibitörlü ve inhibitörsüz EAA oranı (AUCi/AUC) yaklaşık olarak 1 + [I]u/Ki değerine eşittir.

Bağlanmamış konsantrasyonu ilgili yolak için Ki değerini belirgin biçimde aşan inhibitörler (örneğin CYP3A4 için ketokonazol veya itrakonazol), simvastatin gibi duyarlı substratların maruziyetini önemli ölçüde artırabilir.

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

Read next

Half-Maximal Inhibitory ConcentrationYarı Maksimal İnhibitör Konsantrasyon

The concentration of an inhibitor that reduces a specified biological or biochemical activity (e.g. enzyme activity, ligand binding or cell growth) by 50% under the given assay conditions.

 Dissociation ConstantDisosiyasyon Sabiti

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.

 Enzyme InhibitionEnzim İnhibisyonu

A reduction in the activity of a drug-metabolizing enzyme by a co-administered drug or other substance, which lowers the clearance of drugs dependent on that enzyme and raises their concentrations.

 Mechanism-Based InhibitionMekanizma Temelli İnhibisyon

Irreversible or quasi-irreversible enzyme inactivation in which the enzyme converts the inhibitor into a reactive intermediate that binds covalently or tightly to it, so activity returns only as new enzyme is synthesized.

 Drug–Drug Interactionİlaç–İlaç Etkileşimi

A change in the magnitude or duration of a drug's effect, or in its concentrations, caused by the concurrent or prior administration of another drug.

 Perpetrator and Victim DrugsEtkileyen ve Etkilenen İlaçlar

Terms used in drug interaction analysis for the drug that causes an interaction (perpetrator or precipitant) and the drug whose concentrations or effects it alters (victim or object).