Temocapril, A Novel Angiotensin‐Converting Enzyme Inhibitor with Preferential Biliary Excretion

Oguchi, Hisao; Tokoo, Masuo; Tokunaga, Shinichi; Higuchi, Makoto; Hora, Kazuhiko; Furuta, Seiichi

doi:10.1111/j.1527-3466.1995.tb00214.x

Cited by 3 publications

(2 citation statements)

References 22 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our present results with temocapril are consistent with the latter findings. The reasons for the different response of UAE to ACE inhibition are unclear but may involve differences in demographic characteristics of the study groups or the use of ACE inhibitors with different chemical structures and properties (15,28).…”

Section: Discussionmentioning

confidence: 99%

“…Temocapril is a long-lasting ACE inhibitor without a sulfhydryl group in its molecular structure (14,15). After oral administration, temocapril, a prodrug, is rapidly and completely hydrolyzed to yield the pharmacologically active diacid temocaprilat, which is excreted by the dual elimination routes of hepatobiliary and renal clearance (15).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of Long-Term Therapeutic Effect of an ACE Inhibitor, Temocapril, with That of a Diuretic on Microalbuminuria in Non-Diabetic Essential Hypertension.

et al. 2000

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of Long-Term Therapeutic Effect of an ACE Inhibitor, Temocapril, with That of a Diuretic on Microalbuminuria in Non-Diabetic Essential Hypertension.

et al. 2000

View full text Add to dashboard Cite

Long-Term Therapy with an ACE Inhibitor, Temocapril, Reduces Microalbuminuria in Essential Hypertension.

et al. 1998

View full text Add to dashboard Cite

The present study was conducted to prospectively evaluate whether a new ACE inhibitor, temocapril, could modify urinary microalbumin excretion rate (UAE) in a group of hypertensive outpatients who had no evidence of renal impairment. Sixty-three outpatients (32 men and 31 women; mean age, 59.9 ± 1.5 yr) with essential hypertension entered the study, all having been treated for at least 6 mo with dihydropyridine calcium-channel blockers (CCBs: nitrendipine, nisoldipine, or amlodipine). Their blood pressures (BPs) had been controlled to adequate levels with the CCBs. None had overt proteinuria (determined by Albustix) or abnormal serum creatinine levels. After 3 mo of baseline observation under the previous treatment, the subjects were randomly divided into two groups. In group A (n = 31), the previously used CCBs were switched to temocapril, 2 to 4 mg once daily for 12 mo, and BP was controlled at a level equivalent to that during CCB treatment. In group B (n = 32), the subjects were maintained on their previous treatment for a further 12 mo. The effect of temocapril on BP appeared to be clinically similar to that of the previously used CCBs, but it significantly decreased UAE as compared with the previous therapy. In group A, UAE decreased significantly (p < 0.01) from the baseline value of 38.9 + 5.1 mg/g creatinine (Cr) to 22.2 ± 4.2 and 25.3 ± 5.6 mg/g Cr at the 6th and 12th months of temocapril therapy, respectively. In contrast, in group B UAE was unchanged (baseline 39.8 ± 6.6 mg/g Cr; 6 mo, 44.6±6.8; 12 mo, 45.9±7.7). In group A, 17 of 31 patients (54.8%) had abnormal UAE levels (> 29.5 mg/g Cr) during previous therapy with CCBs, but 6 mo after switching to temocapril 25 of these patients (80.6%) had normal UAE (<29.5 mg/g Cr). In group B, 15 of 32 patients (46.9%) had abnormal UAE levels during the observation period, and these abnormal UAE levels remained unchanged; 17 of the 32 patients (53.1%) had abnormal UAE levels after a further 6 mo of continued CCBs therapy. We conclude that long-term therapy with temocapril may provide renal protection by reducing UAE even in hypertensive patients with no evidence of renal impairment. (Hypertens Res 1998; 21: 81-87)

show abstract

Trandolaprilat, an Angiotensin-Converting Enzyme Inhibitor, Is Not Excreted in Bile via and ATP-Dependent Active Transporter(cMOAT).

Shionoiri¹,

Takasaki²,

Minamisawa³

et al. 2001

Hypertens Res

View full text Add to dashboard Cite

Trandolapril is the prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It has been proposed that its active metabolite, trandolaprilat, is mainly excreted in bile, but this has not been clearly demonstrated. Recently it has been reported that temocaprilat, an active metabolite of the ACE inhibitor temocapril, is effectively excreted in bile via an ATP-dependent active transporter (canalicular multispecific organic anion transporter: cMOAT). To investigate whether trandolaprilat has the pharmacological ability to affect the cMOAT system in a manner similar to temocaprilat. The lipophilicity of trandolaprilat and temocaprilat was measured to determine the n-octanol-water partition coefficients. The dose-dependent inhibition of the up-take of [3H]-estradiol-17beta-D-glucuronide and [3H]-2,4-dinitrophenyl-S-glutathione, which are good substrates for cMOAT, in canalicular membrane vesicles (CMVs) prepared from Sprague-Dawley rats was determined in the presence of trandolaprilat and temocaprilat. The partition coefficient of trandolaprilat (log Po/w - 1.1) was about 30 times higher than that of temocaprilat (log Po/w - 2.5). The uptake of [3H]-estradiol-17beta-D-glucuronide and [3H]-2,4-dinitrophenyl-S-glutathione was dose-dependently inhibited by the presence of temocaprilat, but trandolaprilat had no effect on the transport of [3H]-estradiol-17beta-D-glucuronide or [3H]-2,4-dinitrophenyl-S-glutathione into CMVs even at concentrations as high as 200 microM. It could be concluded that trandolaprilat has a higher lipophilicity than temocaprilat. But the hepatobiliary excretion system via cMOAT may not contribute to the excretion of trandolaprilat in bile.

show abstract

Temocapril, A Novel Angiotensin‐Converting Enzyme Inhibitor with Preferential Biliary Excretion

Cited by 3 publications

References 22 publications

Comparison of Long-Term Therapeutic Effect of an ACE Inhibitor, Temocapril, with That of a Diuretic on Microalbuminuria in Non-Diabetic Essential Hypertension.

Comparison of Long-Term Therapeutic Effect of an ACE Inhibitor, Temocapril, with That of a Diuretic on Microalbuminuria in Non-Diabetic Essential Hypertension.

Long-Term Therapy with an ACE Inhibitor, Temocapril, Reduces Microalbuminuria in Essential Hypertension.

Trandolaprilat, an Angiotensin-Converting Enzyme Inhibitor, Is Not Excreted in Bile via and ATP-Dependent Active Transporter(cMOAT).

Contact Info

Product

Resources

About