Pharmacokinetics

First-Pass Effect

TRİlk Geçiş Etkisi
Also known as:First-pass metabolism · presystemic metabolism · presystemic elimination

The metabolism of a drug in the liver (or gut wall) before it reaches systemic circulation, often reducing the bioavailability of orally administered drugs.

Formula

F = Fa × Fg × Fh Fh = 1 − EH

In depth

After absorption, a drug passes through enterocytes, which express CYP3A4 and efflux transporters such as P-glycoprotein, and then through the liver via the portal vein. Oral bioavailability is the product of the fraction absorbed (Fa), the fraction escaping gut-wall metabolism (Fg) and the fraction escaping hepatic extraction (Fh = 1 − EH). Drugs with extensive first-pass metabolism include glyceryl trinitrate, lidocaine, morphine, propranolol, verapamil and simvastatin.

First-pass metabolism is avoided by sublingual, buccal, transdermal, inhaled and parenteral administration, and partly by the rectal route. It varies widely between individuals and is altered by liver disease, portosystemic shunting, food and interacting enzyme inhibitors or inducers.

Clinical pearl

Inhibition of intestinal and hepatic CYP3A4 (e.g. by grapefruit juice, clarithromycin or ketoconazole) can markedly increase exposure to oral substrates with extensive first-pass metabolism, such as simvastatin, raising the risk of myopathy.

Example drugs

glyceryl trinitrate Lidocaine Morphine Propranolol Verapamil Simvastatin
TRIn Turkish

İlk Geçiş Etkisi

Oral yolla verilen ilacın sistemik dolaşıma ulaşmadan önce karaciğerde (veya bağırsak duvarında) metabolize olması; genellikle biyoyararlanımı azaltır.

Absorpsiyondan sonra ilaç, CYP3A4 ve P-glikoprotein gibi efluks taşıyıcılarını içeren enterositlerden ve ardından portal ven aracılığıyla karaciğerden geçer. Oral biyoyararlanım; absorbe edilen kesir (Fa), bağırsak duvarı metabolizmasından kurtulan kesir (Fg) ve hepatik ekstraksiyondan kurtulan kesrin (Fh = 1 − EH) çarpımıdır. Yoğun ilk geçiş metabolizmasına uğrayan ilaçlar arasında gliseril trinitrat, lidokain, morfin, propranolol, verapamil ve simvastatin sayılabilir.

İlk geçiş metabolizmasından dil altı, bukkal, transdermal, inhalasyon ve parenteral uygulamayla kaçınılır; rektal yol ise bu etkiyi kısmen azaltır. İlk geçiş etkisi bireyler arasında büyük farklılık gösterir; karaciğer hastalığı, portosistemik şant, besinler ve etkileşen enzim inhibitörleri veya indükleyicileri tarafından değiştirilir.

Bağırsak ve karaciğer CYP3A4'ünün inhibisyonu (örneğin greyfurt suyu, klaritromisin veya ketokonazol ile), simvastatin gibi yoğun ilk geçiş metabolizmasına uğrayan oral substratlara maruziyeti belirgin şekilde artırarak miyopati riskini yükseltebilir.

Diğer adları:İlk geçiş metabolizması · presistemik metabolizma · presistemik eliminasyon
Updated 24.09.2026 43 views Educational reference — verify against current sources before clinical use.

Read next

BioavailabilityBiyoyararlanım

The fraction of an administered dose that reaches the systemic circulation unchanged, and the rate at which it does so; by definition, bioavailability is 1 (100%) for an intravenous dose.

 Hepatic Extraction RatioHepatik Ekstraksiyon Oranı

The fraction of drug entering the liver in the blood that is irreversibly removed during a single pass through the organ, ranging from 0 (no extraction) to 1 (complete extraction).

 Sublingual AdministrationDil Altı Uygulama

Administration of a drug under the tongue, where it dissolves and is absorbed through the oral mucosa directly into the systemic venous circulation, bypassing hepatic first-pass metabolism.

 CYP3A4CYP3A4

The most abundant cytochrome P450 isoform in the human liver and small-intestinal epithelium, responsible for the oxidative metabolism of a large proportion of clinically used drugs.

 Grapefruit Juice InteractionGreyfurt Suyu Etkileşimi

An interaction in which furanocoumarins in grapefruit juice irreversibly inhibit intestinal CYP3A4, increasing the oral bioavailability of drugs that undergo extensive first-pass metabolism by this enzyme.

 P-glycoproteinP-glikoprotein

An ATP-dependent efflux transporter (ABCB1, MDR1) that pumps a wide range of drugs out of cells, limiting their intestinal absorption and brain entry and promoting their biliary and renal excretion.