Pharmacokinetics of temocapril hydrochloride, a novel angiotensin converting enzyme inhibitor, in renal insufficiency.
The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I). The pharmacokinetic parameters of the active diacid metabolite, including Cmax, AUC and half-life (t1/2), showed only slight changes between the three groups: AUC (0-inaffinity) was significantly larger in Group III than Group I, and t1/2 tended to be prolonged in Group III, but the change was not significant. The urinary recovery of the diacid was significantly decreased in Group III. (Group I, 28.1%, Group II, 21.6%, Group III, 12.8%). Compared with other ACE inhibitors, which are mainly excreted through the kidney, the plasma concentration of the active diacid metabolite was hardly influenced by renal function. It was speculated that lowering of the dose of temocapril might be recommended only in patients with severe renal insufficiency.
Nakashima
M
M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Yamamoto
J
J
Shibata
M
M
Uematsu
T
T
Shinjo
H
H
Akahori
T
T
Shioya
H
H
Sugiyama
K
K
Kawahara
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D011355:Prodrugs / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000378:metabolism*; D013841:Thiazepines / Q000493:pharmacokinetics*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011355:Prodrugs; D013841:Thiazepines; C055603:temocapril hydrochloride