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English to Turkish: A genetic variant, Tacrolimus and rheumatoid arthritis General field: Medical Detailed field: Medical: Pharmaceuticals
Source text - English ABCB1 genetic variant and its associated tacrolimus pharmacokinetics affect renal function in patients with rheumatoid arthritis.
Naito T1, Mino Y2, Aoki Y3, Hirano K2, Shimoyama K4, Ogawa N4, Kagawa Y5, Kawakami J2.
Abstract
BACKGROUND:
This study aimed to evaluate the blood exposure of and clinical responses to tacrolimus based on genetic variants of CYP3A5 and ABCB1 in patients with rheumatoid arthritis.
METHODS:
Seventy rheumatoid arthritis patients treated with oral tacrolimus once daily were enrolled. Blood concentrations of tacrolimus and its major metabolite 13-O-demethylate at 12h after dosing were determined. The relationships between the tacrolimus pharmacokinetics and efficacy, renal function, and CYP3A5 and ABCB1 genotypes were evaluated.
RESULTS:
Dose-normalized blood concentration of tacrolimus was significantly higher in the CYP3A5*3/*3 group than in the *1 allele carrier group. A lower metabolic ratio of 13-O-demethylate to tacrolimus was observed in the CYP3A5*3/*3 group. The ABCB1 3435TT group had higher dose-normalized blood concentrations of tacrolimus and 13-O-demethylate. The blood tacrolimus concentration was inversely correlated with the estimated glomerular filtration rate (eGFR). ABCB1 C3435T but not CYP3A5 genotype had decreased eGFR. Patients lacking the CYP3A5*3 allele had a higher incidence of tacrolimus withdrawal.
CONCLUSION:
CYP3A5*3 increased the blood exposure of tacrolimus through its metabolic reduction. ABCB1 C3435T led to a higher blood exposure of tacrolimus and its major metabolite. The ABCB1 genetic variant and its associated tacrolimus pharmacokinetics affected renal function in rheumatoid arthritis patients.
KEYWORDS:
ABCB1; CYP3A5; Genetic variant; Renal function; Rheumatoid arthritis; Tacrolimus
Translation - Turkish ABCB1 genetik varyantı ve bununla ilişkili takrolimus farmakokinetiği romatoid artrit hastalarında böbrek fonksiyonunu etkilemektedir.
Naito T1, Mino Y2, Aoki Y3, Hirano K2, Shimoyama K4, Ogawa N4, Kagawa Y5, Kawakami J2.
Özet
GENEL BİLGİLER:
Bu çalışmada romatoid artriti bulunan hastalarda CYP3A5 ve ABCB1 genetik varyantlarına dayanılarak kan yoluyla takrolimus maruziyetinin ve buna verilen klinik yanıtların değerlendirilmesi amaçlanmıştır.
YÖNTEMLER:
Çalışmaya günde bir kez oral yolla takrolimus tedavisi alan yetmiş romatoid artrit hastası dahil edilmiştir. Dozlamadan 12 saat sonra takrolimusun ve ana metaboliti olan 13-O-demetilatın kan konsantrasyonları belirlenmiştir. Takrolimus farmakokinetiği ve etkililiği, böbrek fonksiyonu ve CYP3A5 ile ABCB1 genotipleri arasındaki ilişkiler değerlendirilmiştir.
BULGULAR:
Doz normalleştirmesi yapılan takrolimusun kan konsantrasyonu CYP3A5*3/*3 grubunda *1 alleli taşıyan gruba göre anlamlı ölçüde yüksek bulunmuştur. CYP3A5*3/*3 grubunda 13-O-demetilat/takrolimus metabolik oranı daha düşük olarak gözlenmiştir. ABCB1 3435TT grubunda doz bakımından normalleştirilmiş daha yüksek takrolimus ve 13-O-demetilat kan konsantrasyonları görülmüştür. Kan takrolimus konsantrasyonu hesaplanan glomerüler filtrasyon hızı (eGFR) ile ters orantılı olmuştur. ABCB1 C3435T genotipinde azalmış eGFR bulunmuş; fakat CYP3A5 genotipinde bu bulguya rastlanmamıştır. CYP3A5*3 allelinden yoksun hastalarda daha yüksek takrolimus geri çekilmesi insidansı görülmüştür.
SONUÇ:
CYP3A5*3, metabolik indirgeme aracılığıyla kan takrolimus maruziyetini artırmıştır. ABCB1 C3435T, daha yüksek kan takrolimusu ve ana metaboliti maruziyetine yol açmıştır. ABCB1 genetik varyantı ve bu varyantın konuyla ilişkili takrolimus farmakokinetiği romatoid artrit hastalarında böbrek fonksiyonunu etkilemiştir.
ANAHTAR KELİMELER:
ABCB1; CYP3A5; Genetik varyant; Böbrek fonksiyonu; Romatoid artrit; Takrolimus
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Translation education
Bachelor's degree - Istanbul University (Biomedical sciences)
Experience
Years of experience: 9. Registered at ProZ.com: Jun 2013.
As the daughter of a bilingual mother, I enjoy the challenge of translating and find that my academic background on biomedical sciences and neuroscience compliments my linguistic abilities enabling me to perform professional tasks quickly and accurately. I find my work in translating interesting and I enjoy the tasks very much. I believe that translation is a profession which links people from various cultures and societies and further improves cross-cultural understanding. Therefore, working as a translator offers me the privilege of increasing socialization and globalization through reading and writing. N. Ceren Sumer
