Dyphylline prodrugs: plasma hydrolysis and dyphylline release in rabbits.
Ester hydrolysis of prodrugs of dyphylline [7-(2,3-dihydroxypropyl)theophylline] followed first-order kinetics in both human and rabbit plasma. Rate constants were estimated by linear regression analysis of initial conversion rates, determined at different initial prodrug concentrations. Release of dyphylline from different prodrugs was 1.3 to 13 times faster in rabbit plasma than human plasma. However, relative rates of drug release (lability order) followed the same patterns in rabbit and human plasma. Dyphylline concentrations in rabbit plasma were extended slightly following intravenous administration of dyphylline 2',3'-dipivaloate. Oral dosing of the prodrug in rabbits greatly sustained plasma dyphylline concentrations.
Huang
H P
HP
Warner-Lambert Company, Morris Plains, NJ 07950.
Ayres
J W
JW
D000818:Animals; D004400:Dyphylline / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D013045:Species Specificity; D013806:Theophylline / Q000031:analogs & derivatives*
D011355:Prodrugs; D004400:Dyphylline; D013806:Theophylline