title: Pharmacokinetics and pharmacodynamics of a sustained-release biodegradable pellet containing imidapril, a new angiotensin-converting enzyme inhibitor in spontaneously hypertensive rats.
abstract: The pharmacokinetics and pharmacodynamics (PK/PD) of a sustained-release biodegradable pellet containing imidapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated in comparison with those of an osmotic pump in male spontaneously hypertensive rats (SHRs). A pellet was prepared from copolymer of DL-lactic acid and glycolic acid by the melt-pressing technique. Imidapril was released in vitro from the pellet at an approximately zero-order rate and the release profile was similar to that of the osmotic pump. Imidapril was administered subcutaneously via a pellet or an osmotic pump implanted under the skin in the back of SHRs. Plasma concentrations of imidaprilat as an active metabolite of imidapril, plasma ACE activity and systolic blood pressure (SBP) were determined periodically. The plasma concentration of imidaprilat during the administration of a pellet was maintained for 4 weeks, and the plasma concentration profile was close to that of the osmotic pump. Both groups of pellet and osmotic pump significantly inhibited plasma ACE activity and reduced SBP for 4 weeks, and these action profiles were similar in both groups. In addition, in vivo release profile of the pellet was close to the in vitro release profile, and the in vivo release profiles of the pellet and the osmotic pump were similar to each other. From these results, it was found that the PK/PD of a biodegradable pellet were close to those of the osmotic pump, and it was shown that the pellet may be a useful system to maintain the plasma concentration of imidaprilat for a long time.
authors.affiliation: Analytical Research Laboratory, Tanabe Seiyaku, Osaka, Japan. kenta-y@tanabe.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Yamanaka
authors.forename: K
authors.initials: K
authors.lastname: Tagawa
authors.forename: K
authors.initials: K
authors.lastname: Murata
authors.forename: K
authors.initials: K
authors.lastname: Banno
authors.forename: T
authors.initials: T
authors.lastname: Sato
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001673:Biodegradation, Environmental; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004343:Drug Implants; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D048289:Imidazolidines; D015918:Infusion Pumps, Implantable; D008297:Male; D009997:Osmotic Pressure; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D007093:Imidazoles; D048289:Imidazolidines; C065166:imidapril