İlaç metabolizmasında rol oynayan enzimlerin aktivitelerinin belirlenmesinde in vivo prob ilaç kullanımı

Amaç: Bu derlemede, ilaç metabolizmasında rol oynayan enzimlerin aktivitelerinin belirlenmesinde in vivo prob ilaçların kullanımları hakkında bilgi verilmiştir. Ana bulgular: İlaç metabolizmasında görevli enzimler çeşitli ksenobiyotiklerin biyotransformasyonunda da önemli rol oynar. Dokularda enzim sentezindeki farklılıklara bağlı olarak çoğu ilacın farmakokinetik ve farmakodinamiğinde ve toksik maddelere duyarlılıkta bireylerarası ve etnik farklılıklar gösterilmiştir. Enzim aktivitelerinin belirlenmesinde kullanılan birçok metot vardır. Bunlar, enzim düzeylerinin ölçülmesi (direkt) ve in vivo prob ilaç kullanımı (indirekt) ile fenotipin belirlenmesi ve genotipik metotlar olarak ayrılabilir. Genotipik ve direkt metotların bazı sınırlamaları olduğu için enzim aktivitesinin belirlenmesinde sıklıkla prob ilaçlar kullanılır. İn vivo prob ilaç kullanımı farmakokinetik farklılık, bireysel dozaj rejimi, ilaç etkileşimleri, ilaç toksisitesi ve ksenobiyotiklere duyarlılık gibi klinik farmakoloji ve toksikoloji yönünden ve enzimlerin sentezlendiği organların metabolik kapasitelerinin belirlenmesi açısından önemlidir. Sonuç: Prob ilaçlar, klinik farmakoloji ve toksikoloji alanındaki çalışmalarda kullanılabilme potansiyeline sahiptir.

Anahtar Kelimeler:

Enzim aktivasyonu, Fenotip, Biyobelirteçler, farmakolojik

Use of in vivo probe drugs in the determination of activities of drug metabolizing enzymes

Objective: In this review, the knowledge was given about the use of in vivo probe drugs in the determination of drug metabolizing enzyme activities. Main findings: Drug metabolizing enzymes play an important role in the biotransformation of various xenobiotics. Inter-individuals and ethnics variability have been demonstrated in the pharmacokinetics and pharmacodynamics of many drugs and in susceptibility to toxic substances because of variations in the expression of different enzymes in tissues. A wide range of methods for the determination of enzyme activities is available. These can be divided into those concerned with phenotype determination, either by measurement of enzyme levels (direct) or use of in vivo probe drugs (indirect) and genotyping methods. Because of some limitations of genotyping and direct methods, probe drugs are often used in the determination of enzyme activities. Use of in vivo probe drugs is important for evaluations of several aspects of clinical pharmacology and toxicology such as pharmacokinetic variability, individual dosage regimen, drug interactions, drug toxicity and the susceptibility to xenobiotics and for the determination of metabolic capacities of organs expressing enzymes. Conclusion: Probe drugs have the potential use in clinical pharmacology and toxicology studies.

Keywords:

Enzyme Activation, Phenotype, Biomarkers, Pharmacological,

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