Title:Phosphate Prodrugs: An Approach to Improve the Bioavailability of
Clinically Approved Drugs
Volume: 31
Issue: 3
关键词:
磷酸盐，前药，溶解度，药代动力学，生物利用度，药物不良反应，药效学，磷酸。
摘要: The phosphate prodrug approach has emerged as a viable option for increasing
the bioavailability of a drug candidate with low hydrophilicity and poor cell membrane
permeability. When a phosphoric acid moiety is attached to the parent drug, it results in a
several-fold elevation in aqueous solubility which helps to achieve desired bioavailability
of the pharmaceutically active parental molecule. The neutral phosphate prodrugs have
rapid diffusion ability through the plasma membrane as compared to their charged counterpart.
The presence of phosphate mono ester breaking alkaline phosphatase (ALP) enzyme
throughout the whole human body, is the main consideration behind the development
of phosphate prodrug strategy. The popularity of this phosphate prodrug strategy is
increasing nowadays due to the fulfillment of different desired pharmacokinetic characteristics
required to get pharmaceutical and therapeutic responses without showing any serious
adverse drug reactions (ADR). This review article mainly focuses on various phosphate
prodrugs synthesized within the last decade to get an improved pharmacological response
of the parent moiety along with various preclinical and clinical challenges associated
with this approach. Emphasis is also given to the chemical mechanism to release the
parent moiety from the prodrug.
