Toxicodynamic analysis of inflammatory reactions by an angiotensin converting enzyme inhibitor (lisinopril) in guinea-pig skin.
There have been reports of rash and angioedema in the treatment of hypertension with angiotensin converting enzyme (ACE) inhibitors. To evaluate the inflammatory reaction, we continuously infused lisinopril for three days into the peritoneal cavity of ovalbumin-sensitized guinea-pigs and tested intradermal inflammation with ovalbumin. Inflammatory responses were measured in two perpendicular directions serially, and the areas of rash were used as an index of inflammatory reaction induced by lisinopril. Inflammatory responses were dose-dependently enhanced by treatment with lisinopril. Plasma concentration of lisinopril required to produce 50% of the maximum potentiation of the inflammatory reaction in guinea-pig skin was 40 times plasma unbound concentration after the clinical treatment of lisinopril in patients.
Ito
K
K
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Ito
K
K
Sawada
Y
Y
Iga
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D003875:Drug Eruptions / Q000473:pathology*; D005260:Female; D006168:Guinea Pigs; D017706:Lisinopril / Q000493:pharmacokinetics / Q000633:toxicity*; D010047:Ovalbumin / Q000276:immunology; D011485:Protein Binding; D011863:Radioimmunoassay; D012867:Skin / Q000473:pathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001798:Blood Proteins; D010047:Ovalbumin; D017706:Lisinopril