Transdermal penetration of cytarabine and its 5'-O alkyl ester derivatives.
The purpose of this study was to synthesize and determine the in vitro transdermal penetration of cytarabine and its 5'-alkyl esters and to establish a correlation, if any, with selected physicochemical properties. The n-alkyl esters were synthesized by acylation of cytarabine (1) at its pharmacophoric 5'-OH. The transdermal flux values of (1) and its esters were determined in vitro using Franz diffusion cell methodology. Aqueous solubility and log D (pH 7.4) values were determined and assessed for correlation to transdermal flux. An inverse relation was observed between the water solubility (Sw) and log D values. Of all esters, (4) exhibited the highest flux value of 22.2 nmol x cm(-2) x h(-1), which is significantly different to that of the parent drug cytarabine (3.70 nmol x cm(-)2 x h(-1)). No trend was found between water solubility and flux values.
Legoabe
Lesetja J
LJ
Unit for Drug Research and Development, North West University, Private Bag X 6001, Potchefstroom, 2520, South Africa. lesetja.legoabe@nwu.ac.za
Breytenbach
Jaco C
JC
N'Da
David D
DD
Breytenbach
J Wilma
JW
D000279:Administration, Cutaneous; D002627:Chemistry, Physical; D003561:Cytarabine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015394:Molecular Structure; D012867:Skin / Q000737:chemistry / Q000187:drug effects*; D012869:Skin Absorption / Q000187:drug effects*; D012882:Skin Tests; D012995:Solubility; D013237:Stereoisomerism; D014018:Tissue Distribution
D004952:Esters; D003561:Cytarabine