A radioimmunoassay for MC-838 (altiopril calcium), a novel angiotensin-converting enzyme inhibitor.
A radioimmunoassay was developed for a new, potent inhibitor of angiotensin-converting enzyme (ACE; EC 3.4.15.1), calcium(-)-N-[(S)-3-[(N-cyclohexylcarbonyl-D-alanyl)thio]-2-methyl- propionyl]-L-prolinate (MC-838, altiopril calcium). The antiserum was obtained by immunizing rabbits with MC-838-bovine serum albumin (BSA) conjugate. MC-838-L-tyrosine labeled with 125I and purified by thin-layer chromatography was used as a tracer. The assay sensitivity was 0.1 ng/ml, the average intra-assay coefficient of variation was 7.9%, and the average inter-assay coefficient of variation was 13.7%. The antiserum was specific for MC-838, showing only slight crossreactivity with degradation products of MC-838. After a single oral dose of MC-838 (2 mg/kg), radioimmunoassay of MC-838 canine serum demonstrated rapid absorption from the gastrointestinal tract with a peak level of 40.6 ng/ml. The decline in serum concentration was a biphasic decay, with a half-life of 80 min during rapid falloff followed by a slower decline.
Hinohara
Y
Y
Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Japan.
Tanaka
S
S
Wakabayashi
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis* / Q000097:blood; D000818:Animals; D004285:Dogs; D011392:Proline / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood; D011817:Rabbits; D011863:Radioimmunoassay; D015203:Reproducibility of Results
D000806:Angiotensin-Converting Enzyme Inhibitors; C048961:MC 838; D011392:Proline