Inhibition of serum angiotensin-converting enzyme in rabbits after intravenous administration of enalaprilat-loaded intact erythrocytes.
Encapsulation of drugs in intact erythrocytes, because of the profound characteristics of these natural microspheres, has gained considerable attention in recent years. In this study, the inhibition time courses of serum angiotensin-converting enzyme (ACE) activity after intravenous administration of enalaprilat encapsulated in intact erythrocytes was evaluated and compared with free drug, in a rabbit model. Three groups of animals each received free drug, drug-loaded erythrocytes or sham-encapsulated erythrocytes. Serum ACE activity was determined in each case using the synthetic substrate hippuryl-histidyl-leucine and quantitation of the hippuric acid released by a developed and validated HPLC method. The serum ACE inhibition profiles in the three groups showed that the encapsulated drug inhibited the serum ACE more slowly, more efficiently, over a considerably longer time and in a more reproducible manner, than the free drug or sham-encapsulated erythrocytes. We conclude that the erythrocytes can serve as efficacious slow-release drug carriers for enalaprilat in circulation.
Hamidi
M
M
Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Iran.
Tajerzadeh
H
H
Dehpour
A R
AR
Ejtemaee-Mehr
S
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D003692:Delayed-Action Preparations; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology*; D004912:Erythrocytes; D007262:Infusions, Intravenous; D007700:Kinetics; D008863:Microspheres; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits; D015203:Reproducibility of Results
D000806:Angiotensin-Converting Enzyme Inhibitors; D003692:Delayed-Action Preparations; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat