A Minireview: Usefulness of Transporter-Targeted Prodrugs in Enhancing Membrane Permeability

Abstract

Orally administered drugs are categorized into 4 classes depending on the solubility and permeability in a Biopharmaceutics Classification System. Prodrug derivatization is one of feasible approaches in modifying the physicochemical properties such as low solubility and low permeability without changing the in vivo pharmacological action of the parent drug. In this article, prodrug-targeted solute carrier (SLC) transporters were searched randomly by PubMed. Collected SLC transporters are amino acid transporter 1, bile acid transporter, carnitine transporter 2, glucose transporter 1, peptide transporter 1, vitamin C transporter 1, and multivitamin transporter. The usefulness of transporter-targeted prodrugs was evaluated in terms of membrane permeability, stability under acidic condition, and conversion to the parent drug. Among prodrugs collected, peptide transporter-targeted prodrugs exhibited the highest number, and some prodrugs such as valaciclovir and valganciclovir are clinically available. ATP-binding cassette efflux transporter, P-glycoprotein (P-gp), reduces the intestinal absorption of lipophilic P-gp substrate drugs, and SLC transporter-targeted prodrugs of P-gp substrate drugs circumvented the P-gp-mediated efflux transport. Thus, SLC transporter-targeted prodrug derivatization seems to be feasible approach to increase the oral bioavailability by overcoming various unwanted physicochemical properties of orally administered drugs, although the effect of food on prodrug absorption should be taken into consideration.

Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens

“… 121 It has been found that in the intestinal cells, coronavirus increases the glucose absorption through sodium ion-dependent glucose transporters known as SGLT1. 122 In DENV infected cells, it has been successfully demonstrated that treatment of infected cells with sodium oxamate and 2-deoxy-D-glucose (2DG) results in inhibition of glycolysis and thus, in DENV replication. 123 , 124 …”

Recent advances in understanding prodrug transport through the SLC15 family of proton-coupled transporters

“…Modifying drugs to improve their pharmacokinetic properties results in so-called prodrugs, which are generally bioreversible derivatives of the parent drug molecules that undergo an enzymatic or chemical transformation in vivo to release the active parent drug [6]. Over the past 10 years, significant effort has been made in the design of novel prodrug molecules with improved pharmacokinetic profiles [7,8]. One successful approach has been to use amino acids as promoieties, as these confer several advantages on the parent compound, including increased water solubility and the targeting of intestinal SLC transporters for oral drug delivery [9].…”

Evaluation of Dissolution Profiles of a Newly Developed Solid Oral Immediate-Release Formula Containing Alpha-Lipoic Acid

“…The test formula 600 mg sample solution-tablet, batch number S580317 In a Biopharmaceutics Classification System (BCS), orally administered drugs are categorized into four classes depending on the solubility and permeability. BCS class I drugs exhibit high solubility and high permeability, class II drugs low solubility and high permeability, class III drugs high solubility and low permeability, and class IV drugs low solubility and low permeability [85,86]. ALA is found in BSC II [25] and tested according to the USP ALA tablets Monograph.…”