What should be considered on design of a colon-specific prodrug?

IMPORTANCE OF THE FIELD: Generally, a prodrug, a pharmacologically inactive derivative of an active drug, is designed to modulate pharmacokinetic properties of the parent drug. Targeted distribution of an orally administered drug at the large intestine confers therapeutic advantages on treatment of colonic diseases, peptide and protein therapy and chronotherapy. AREAS COVERED IN THIS REVIEW: To achieve such distribution control in the gastrointestinal tract, the adoption of the prodrug concept gives birth to a colon-specific prodrug. The requirement for a prodrug to be colon-specific is described along with the necessary and sufficient conditions of drugs for conversion to a colon-specific prodrug. The known and previously unnoticed factors that negatively influence therapeutic activity and reproducibility of a colon-specific prodrug are presented with suggestions to minimize the negative influence. WHAT THE READER WILL GAIN: This review provides tactics to satisfy the requirements for being colon-specific and the potential strategies to circumvent obstacles in developing an efficient colon-specific prodrug. TAKE HOME MESSAGE: On design of a colon-specific prodrug, one should take into consideration not only delivery of a drug to the target site, but also the therapeutic effectiveness there.