Drug Metabolism & Transporters

Prodrug

TRÖn İlaç (Prodrug)
Also known as:Pro-drug · Precursor drug

A pharmacologically inactive or weakly active compound that is converted in the body, enzymatically or chemically, into the active drug.

In depth

Prodrugs are designed to improve oral absorption (e.g. ester prodrugs such as enalapril, valaciclovir and oseltamivir), increase solubility (fosphenytoin), prolong action or target activation to a tissue. Some established drugs were recognized as prodrugs only after their introduction, such as codeine (partly converted to morphine by CYP2D6) and clopidogrel (activated in two oxidative steps in which CYP2C19 plays a major role).

Because activation depends on specific enzymes, prodrug response is sensitive to genetic polymorphisms and enzyme inhibition: in contrast to active drugs, impaired metabolism reduces rather than increases the effect, while enhanced activation may cause toxicity.

Clinical pearl

CYP2D6 ultrarapid metabolizers can form dangerous amounts of morphine from codeine (and excess active metabolite from tramadol), whereas CYP2C19 poor metabolizers derive reduced antiplatelet effect from clopidogrel.

Example drugs

Codeine Clopidogrel Enalapril Valaciclovir Levodopa Fosphenytoin
TRIn Turkish

Ön İlaç (Prodrug)

Vücutta enzimatik ya da kimyasal yolla aktif ilaca dönüştürülen, farmakolojik olarak inaktif veya zayıf aktif bir bileşiktir.

Ön ilaçlar oral absorpsiyonu iyileştirmek (ör. enalapril, valasiklovir ve oseltamivir gibi ester ön ilaçlar), çözünürlüğü artırmak (fosfenitoin), etki süresini uzatmak ya da aktivasyonu belirli bir dokuya yönlendirmek amacıyla tasarlanır. Kodein (CYP2D6 ile kısmen morfine dönüşür) ve klopidogrel (CYP2C19'un önemli rol oynadığı iki basamaklı oksidasyonla aktive olur) gibi bazı yerleşik ilaçların ön ilaç olduğu ise kullanıma girdikten sonra anlaşılmıştır.

Aktivasyon belirli enzimlere bağlı olduğundan ön ilaç yanıtı genetik polimorfizmlere ve enzim inhibisyonuna duyarlıdır: aktif ilaçların tersine, bozulmuş metabolizma etkiyi artırmaz, azaltır; aşırı aktivasyon ise toksisiteye yol açabilir.

CYP2D6 ultra hızlı metabolizörlerinde kodeinden tehlikeli miktarda morfin (tramadolden de aşırı miktarda aktif metabolit) oluşabilir; CYP2C19 zayıf metabolizörlerinde ise klopidogrelin antiplatelet etkisi azalır.

Diğer adları:Prodrug · Öncül ilaç
Updated 24.09.2026 0 views Educational reference — verify against current sources before clinical use.

Read next

Active MetaboliteAktif Metabolit

A product of drug metabolism that has pharmacological activity of its own, which may be similar to, greater than or different from that of the parent drug.

 Phase I MetabolismFaz I Metabolizma

Functionalization reactions, mainly oxidation, reduction and hydrolysis, that introduce or unmask a polar group such as –OH, –NH2 or –COOH on a drug molecule.

 CYP2D6CYP2D6

A highly polymorphic cytochrome P450 enzyme that metabolises a large number of drugs, including several opioids and antidepressants, and activates key prodrugs.

 CYP2C19CYP2C19

A cytochrome P450 enzyme that activates the prodrug clopidogrel to its antiplatelet metabolite and also metabolises proton pump inhibitors and several other drugs.

 Ultrarapid MetabolizerUltra Hızlı Metabolizör

A CPIC phenotype for a person with increased drug-metabolising enzyme activity, often from a gene duplication or an increased-function allele, above the normal metabolizer range.

 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.