Journal of Literature Pharmacy Sciences

Kiralite Kavramı ve İlaç Güvenliliği İlişkisi: Geleneksel Derleme
The Concept of Chirality and its Association with Drug Safety: Traditional Review
Ayfer BAHARa, N. İpek KIRMIZI SÖNMEZb, Caner VIZDIKLARa, Volkan AYDINc, Ahmet AKICIa
aMarmara Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji ABD, İstanbul, Türkiye
bİstanbul Medipol Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji ABD, İstanbul, Türkiye
cİstanbul Medipol Üniversitesi Uluslararası Tıp Fakültesi, Tıbbi Farmakoloji ABD, İstanbul, Türkiye
J Lit Pharm Sci. 2022;11(2):77-85
doi: 10.5336/pharmsci.2022-88233
Article Language: TR
Full Text
ÖZET
 Literatürde biyolojik sistemlerde yer alan objelerin ayna görüntüleriyle örtüşmeme durumları üzerinden ifade edilen kiralite, ilaçların vücutta ortaya çıkardığı etkiler bakımından önemli bir rol oynamaktadır. 1950?li yıllarda sentetik ilaç üretiminde görülen artışla birlikte izomer karışımı formundaki ilaçların piyasada yaygınlaştığı görülmektedir. İlacın yapısında bulunan her bir izomerin, farmakolojik olarak birbirinden farklı etki ve advers ilaç reaksiyonlarına yol açabildiği bilinmektedir. Bu durum, klinikte ilaç etkililiğini olumsuz yönde değişebilmesi riskinin yanı sıra potansiyel güvenlilik sorunlarına da zemin hazırlayabilir. Örneğin farmakovijilans tarihçesinde önemli bir kilometre taşı olan talidomid trajedisinde de farklı klinik sonuçlar alınmasında molekülün farklı izomerlerinin rol oynadığı literatürde gösterilmiştir. Kiralite kavramı ile ilgili söz konusu gelişmeler ışığında uluslararası sağlık otoriteleri, yeni üretilen ilaçların mümkün olduğunca saf enantiyomer olarak üretilmesi yönünde pek çok tavsiyede bulunmuştur. Farmasötik teknoloji alanında kaydedilen ilerlemelerin de katkısıyla piyasaya giren yeni ilaçlarda saf izomerlerin payı eskiye kıyasla giderek artmıştır. Ayrıca mevcut olan izomer karışımı formundaki ilaçların saflaştırılarak piyasaya sürülmesi prensibine dayanan ?kiral dönüşüm? örnekleri de ilaç pazarında görülmeye başlanmıştır. Hâlihazırda ilaçların saf izomer olarak geliştirilmesi gibi bir zorunluluk bulunmamakla birlikte, izomer karışımlar ile ilgili güvenlilik endişelerinin gelecekte yeni yaklaşımlara kapı aralamasının mümkün olabileceği düşünülmektedir. Bu derlemede; kiralite kavramı ve söz konusu kavramın ilaçlardaki güvenlilik sorunları ile olası ilişkisi ele alınmıştır.

Anahtar Kelimeler: Kiralite; ilaç güvenliliği; farmakovijilans; stereokimya; enantiyomer
ABSTRACT
 Chirality, which is expressed in terms of non-overlapping of mirror images of objects in biological systems, plays an important role for drugs to exert their effects on the body. With the increase in the manufacture of synthetic drugs in the 1950s, drugs in the form of isomeric mixtures became widespread in the market. Each isomer in the structure of the drug can cause pharmacologically different effects and adverse drug reactions. This situation may adversely affect the clinical efficacy of the drug, as well as lay the groundwork for safety problems. For example, in the thalidomide tragedy, which is an important milestone in the history of pharmacovigilance, different isomers of the molecule have been shown to play a role in obtaining different clinical outcomes. In the light of these developments in chirality concept, health authorities have recommended that new drugs be produced as pure enantiomers as much as possible. With the contribution of the advances in pharmaceutical technology, the share of pure isomers in new drugs entering the market has gradually increased. In addition, examples of 'chiral switch' based on the purification of existing isomeric mixture drugs have begun to be introduced. Although there is currently no obligation to develop drugs as pure isomers, it is possible that safety concerns regarding isomeric mixtures will leads to new approaches in the future. In this review, the concept of chirality is discussed from the perspective of its possible relationship with the safety problems in drugs.

Keywords: Chirality; drug safety; pharmacovigilance; stereochemistry; enantiomer
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