Pharmacogenomics

Slow Acetylator

TRYavaş Asetilatör
Also known as:NAT2 Slow Acetylator

A phenotype defined by reduced N-acetyltransferase 2 (NAT2) activity, causing slower inactivation of drugs cleared by acetylation and greater exposure at standard doses.

In depth

NAT2 genetic polymorphism divides patients into slow and rapid (fast) acetylator phenotypes, with slow acetylator frequency varying widely by population. Slow acetylators exposed to isoniazid are at greater risk of peripheral neuropathy and hepatotoxicity, and those on hydralazine or procainamide are at greater risk of drug-induced lupus and other dose-related adverse effects.

Unlike CYP2D6 or CYP2C19, NAT2 acetylator status is not yet part of a formal CPIC dosing guideline for most drugs, but it remains a well-established textbook explanation for interindividual variation in toxicity from these agents, and pyridoxine co-administration is used to mitigate isoniazid neuropathy risk generally.

Clinical pearl

Unexplained isoniazid-related peripheral neuropathy or hydralazine/procainamide-induced lupus-like symptoms should prompt consideration of slow acetylator status as a contributing factor.

Example drugs

Isoniazid Hydralazine Procainamide
TRIn Turkish

Yavaş Asetilatör

N-asetiltransferaz 2 (NAT2) aktivitesinin azalmasıyla tanımlanan; asetilasyon yoluyla temizlenen ilaçların inaktivasyonunun yavaşlamasına ve standart dozlarda daha yüksek maruziyete yol açan bir fenotiptir.

NAT2 genetik polimorfizmi hastaları yavaş ve hızlı asetilatör fenotiplerine ayırır; yavaş asetilatör sıklığı popülasyona göre büyük farklılık gösterir. İzoniazide maruz kalan yavaş asetilatörler periferik nöropati ve hepatotoksisite açısından, hidralazin veya prokainamid kullananlar ise ilaca bağlı lupus ve diğer doza bağlı advers etkiler açısından daha yüksek risk taşır.

CYP2D6 veya CYP2C19'un aksine, NAT2 asetilatör durumu çoğu ilaç için henüz resmi bir CPIC dozlama kılavuzunun parçası değildir; ancak bu ilaçlarla görülen toksisitedeki bireyler arası farklılığı açıklayan, ders kitaplarında yerleşik bir kavram olmaya devam eder ve izoniazid nöropati riskini azaltmak için genel olarak piridoksin birlikte uygulanır.

Açıklanamayan izoniazide bağlı periferik nöropati veya hidralazin/prokainamide bağlı lupus benzeri semptomlar, katkıda bulunan bir etken olarak yavaş asetilatör durumunun akla getirilmesini gerektirir.

Updated 24.09.2026 1 views Educational reference — verify against current sources before clinical use.

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PharmacogenomicsFarmakogenomik

The study of how inherited genetic variation affects an individual's response to drugs, used clinically to guide drug and dose selection.

 Genetic PolymorphismGenetik Polimorfizm

A DNA sequence variation, such as a single-nucleotide change or a copy-number variant, present in more than about 1% of a population.

 Poor MetabolizerZayıf Metabolizör

A CPIC phenotype for a person carrying two non-functional (no-function) alleles of a drug-metabolising enzyme gene, resulting in little or no enzyme activity.

 Phase II MetabolismFaz II Metabolizma

Conjugation reactions in which an endogenous moiety such as glucuronic acid, sulfate, glutathione, an acetyl or a methyl group is attached to a drug or to its phase I metabolite.

 HepatotoxicityHepatotoksisite

Liver injury caused by a drug, herbal or dietary supplement or other chemical, ranging from asymptomatic aminotransferase elevation to cholestasis, hepatitis and acute liver failure.