ArticlePharmaceutical research2003
Absorption rate limit considerations for oral phosphate prodrugs.
Article in Pharmaceutical research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 78 citations in OpenAlex.
- Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.Pharmacotherapy · 2014Trial
- Sol-moiety: Discovery of a water-soluble prodrug technology for enhanced oral bioavailability of insoluble therapeutics.Nature communications · 2024Article
- Encapsulation and release of hydrocortisone from proliposomes govern vaginal delivery.Drug delivery and translational research · 2023Article
- Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP.Journal of medicinal chemistry · 2022Article
- Improving the Pharmacological Properties of Ciclopirox for Its Use in Congenital Erythropoietic Porphyria.Journal of personalized medicine · 2021Article
- The evolution of nucleosidic analogues: self-assembly of prodrugs into nanoparticles for cancer drug delivery.Nanoscale advances · 2021Review
- Innovation in the discovery of the HIV-1 attachment inhibitor temsavir and its phosphonooxymethyl prodrug fostemsavir.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Review
- Novel insights into glucocorticoid replacement therapy for pediatric and adult adrenal insufficiency.Therapeutic advances in endocrinology and metabolism · 2019Review
- Tedizolid phosphate for the treatment of acute bacterial skin and skin-structure infections: an evidence-based review of its place in therapy.Core evidence · 2019Article
- The expanding role of prodrugs in contemporary drug design and development.Nature reviews. Drug discovery · 2018Review
- Development and characterization of nifedipine-amino methacrylate copolymer solid dispersion powders with various adsorbents.Asian journal of pharmaceutical sciences · 2017Article
- Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections.Drug design, development and therapy · 2017Review
- Discovery and Characterization of a Water-Soluble Prodrug of a Dual Inhibitor of Bacterial DNA Gyrase and Topoisomerase IV.ACS medicinal chemistry letters · 2015Article
- Direct inhibitors of InhA are active against Mycobacterium tuberculosis.Science translational medicine · 2015Article
- Mechanistic studies on regioselective dephosphorylation of phosphate prodrugs during a facile synthesis of antitumor phosphorylated 2-phenyl-6,7-methylenedioxy-1H-quinolin-4-one.Molecules (Basel, Switzerland) · 2013Article
- Absorption rate limit considerations for oral phosphate prodrugs.Pharmaceutical research · 2003Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo evaluate the potential of phosphate ester prodrugs to significantly improve the absorptive flux of poorly soluble parent drugs.
methodsAbsorptive transport studies of parent drugs and their prodrugs were carried out in Caco-2 cells. Prodrugs of parent drugs with variable aqueous solubilities were tested: Hydrocortisone-phosphate/Hydrocortisone, Fosphenytoin/phenytoin, TAT-59/DP-TAT-59, and Entacapone phosphate/Entacapone. Additional absorption studies were carried out in rats.
resultsAbsorptive fluxes of DP-TAT-59 and phenytoin increased 9.8 or 3.3-fold after dosing TAT-59 and 500 microM fosphenytoin, respectively. Hydrocortisone's flux did not increase with hydrocortisone-phosphate at 100 microM. Permeability of the highly lipophilic and protein bound compound, DP-TAT-59, was significantly increased with serosal albumin. No permeability increase was observed for the other drugs with albumin. Entacapone phosphate failed to improve the flux of entacapone compared to an entacapone solution, but the prodrug solution did yield higher entacapone plasma levels in rats when compared with an entacapone suspension.
conclusionIdeal phosphate prodrug candidates are characterized by high permeability and low solubility (BCS Class II drugs). For low dose BCS Class II drug candidates, however, no biopharmaceutical advantage may be gained. Phosphate prodrugs of parent drugs with limited permeability may fail. When screening highly lipophilic parent drugs transport studies should be done with albumin.
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