Biomaterial Database

Effects of vehicles and prodrug properties and their interactions on the delivery of 6-mercaptopurine through skin: S6-acyloxymethyl-6-mercaptopurine prodrugs. 1988

R P Waranis, and K B Sloan

Department of Medicinal Chemistry, University of Florida, Gainesville 32610.

A homologous series of S6-acyloxymethyl-6-mercaptopurine (6-mono-6-MP) and two 9-acyloxymethyl-6-mercaptopurine (9-mono-6-MP) prodrugs have been synthesized and characterized. The ability of the 6-mono-6-MP prodrugs to deliver 6-mercaptopurine (6-MP) through hairless mouse skin from isopropyl myristate (IPM) and propylene glycol (PG) has been evaluated. There was a good correlation between the log experimental permeability coefficients from the diffusion data and calculated solubility parameters of the prodrugs. Although there was no statistical difference between the rates of delivery of 6-MP by the acetyl through valeryl 6-mono-6-MP prodrugs from IPM, the butyryl and valeryl prodrugs were significantly better at delivering 6-MP from PG. For a given solubility parameter value, the 6-mono-6-MP prodrugs were less soluble in water and IPM, and more soluble in PG than the previously studied S6,9-bisacyloxymethyl-6-MP (6,9-bis-6-MP) prodrugs. On the other hand, for a given solubility parameter, the 6,9-bis-6-MP prodrugs were generally more effective at delivering 6-MP from IPM and PG. The single 9-mono-6-MP prodrug that was evaluated was much less effective at delivering 6-MP than either the 6-mono- or 6,9-bis-6-MP prodrugs. Thus, it is much less important to mask the imidazole than the thionamide functional group in 6-MP to enhance the topical delivery of 6-MP using a prodrug approach.

UI	MeSH Term	Description	Entries
D008812	Mice, Hairless	Mutant strains of mice that produce little or no hair.	Hairless Mice,Mice, Inbred HRS,Mice, hr,Hairless Mouse,Mice, HRS,Mouse, HRS,Mouse, Inbred HRS,HRS Mice,HRS Mice, Inbred,HRS Mouse,HRS Mouse, Inbred,Inbred HRS Mice,Inbred HRS Mouse,Mouse, Hairless
D009682	Magnetic Resonance Spectroscopy	Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).	In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D011355	Prodrugs	A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.	Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D004058	Diffusion	The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT.	Diffusions
D004355	Drug Stability	The chemical and physical integrity of a pharmaceutical product.	Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012869	Skin Absorption	Uptake of substances through the SKIN.	Absorption, Skin,Intracutaneous Absorption,Intradermal Absorption,Percutaneous Absorption,Transcutaneous Absorption,Transdermal Absorption,Absorption, Intracutaneous,Absorption, Intradermal,Absorption, Percutaneous,Absorption, Transcutaneous,Absorption, Transdermal,Absorptions, Intracutaneous,Absorptions, Intradermal,Absorptions, Percutaneous,Absorptions, Skin,Absorptions, Transcutaneous,Absorptions, Transdermal,Intracutaneous Absorptions,Intradermal Absorptions,Percutaneous Absorptions,Skin Absorptions,Transcutaneous Absorptions,Transdermal Absorptions
D012995	Solubility	The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Solubilities
D014677	Pharmaceutical Vehicles	A carrier or inert medium used as a solvent (or diluent) in which the medicinally active agent is formulated and or administered. (Dictionary of Pharmacy, 1986)	Pharmaceutical Vehicle,Vehicle, Pharmaceutical,Vehicles, Pharmaceutical