Single dose and steady state pharmacokinetics and pharmacodynamics of the ACE‐inhibitor imidapril in hypertensive patients

Harder, Sebastian; Thürmann, Petra A.; Ungethüm, W.

doi:10.1046/j.1365-2125.1998.t01-1-00694.x

Cited by 13 publications

(3 citation statements)

References 12 publications

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“…In contrast to calculated predictions, there was a significant decrease in I 24 and AUC 0–24 from day 1 to day 7 of repeated daily administrations. Studies in people and dogs have shown minimal to no cumulative effects on ACE inhibition with repeated administration . However, the significant decrease in I 24 and AUC 0–24 were unexpected.…”

Section: Discussionmentioning

confidence: 98%

Pharmacodynamic Evaluation of 4 Angiotensin‐Converting Enzyme Inhibitors in Healthy Adult Horses

Afonso

Giguère

Rapoport

et al. 2013

Veterinary Internal Medicne

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Background: Angiotensin-converting enzyme (ACE) inhibitors are used in horses with cardiovascular disorders despite the paucity of available data regarding their efficacy.Hypothesis: The degree of serum ACE inhibition varies considerably between drugs. Animals: Eight healthy adult horses. Methods: Randomized prospective study. Horses were fasted overnight prior to receiving one of 4 ACE inhibitors intragastrically, administered at one of 2 dosages, using a randomized Latin square design (benazepril: 0.5 and 0.25 mg/ kg; ramipril: 0.3 and 0.1 mg/kg; quinapril: 0.25 and 0.125 mg/kg; perindopril: 0.1 and 0.05 mg/kg). Serum ACE activity was measured using a kinetic spectrophotometric method.Results: There was a significant effect of drug and dosage on maximum ACE inhibition (I max ), ACE inhibition 24 hours after administration (I 24h ), and area under the curve (AUC 0-48h ). Benazepril at 0.5 mg/kg resulted in significantly higher I max (86.9 AE 7.0%) and I 24h (60.3 AE 7.9%) compared to the other drugs. There was a significant decrease in indirect blood pressure (BP) over time after administration of each drug, but differences in BP were not significantly different between drugs. Pharmacodynamic variables measured after administration of benazepril to horses with free access to hay were not significantly different from those obtained after fasting. Administration of benazepril orally once daily for 7 days did not result in a cumulative effect on ACE inhibition.Conclusions and Clinical Importance: Of the ACE inhibitors tested, oral benazepril (0.5 mg/kg) is the most effective at inhibiting serum ACE activity in healthy horses.

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Section: Discussionmentioning

confidence: 98%

Pharmacodynamic Evaluation of 4 Angiotensin‐Converting Enzyme Inhibitors in Healthy Adult Horses

Afonso

Giguère

Rapoport

et al. 2013

Veterinary Internal Medicne

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“…Because t max of imidaprilat and enalaprilat is longer than 2 hours (Table II), absorption and de‐esterification of imidapril and enalapril occurred during the dialysis sessions and may have affected plasma concentrations of their active metabolites in this study. However, such contributions are likely minor for the difference of arterial drug concentrations between imidaprilat and enalaprilat because the t max of the 2 drugs are relatively similar 9,16 (Table III). On the other hand, the prodrug still remains in the blood during the dialysis session, and it may be eliminated by the dialysis, which consequently affects the concentration profiles of active metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…We used high‐performance liquid chromatography (HPLC) to measure plasma drug concentration 9,10,16 . A 0.1‐mL volume of 0.25 M hydrochloric acid and 1 mL of 30 mM 1‐decansulfonate were added to each plasma sample (0.5 mL) and vortexed well.…”

Section: Methodsmentioning

confidence: 99%

Clearance of Imidapril, an Angiotensin‐Converting Enzyme Inhibitor, During Hemodialysis in Hypertensive Renal Failure Patients: Comparison With Quinapril and Enalapril

Tsuruoka

Kitoh

Kawaguchi

et al. 2007

The Journal of Clinical Pharma

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The dialyzability of imidaprilat, an active metabolite of the angiotensin-converting enzyme (ACE) inhibitor imidapril, was determined and compared with those of enalaprilat and quinaprilat in hypertensive patients on chronic hemodialysis. Imidapril (5 mg/d, n = 6), enalapril (2.5 mg/d, n = 6), or quinapril (2.5 mg/d, n = 6) was given for at least 8 weeks prior to the trial. During dialysis, enalaprilat, but not imidaprilat or quinaprilat, concentrations in both sides decreased significantly. Compared to enalaprilat, the dialyzabilities of imidaprilat and quinaprilat were significantly lower (dialyzer clearance [mL/min/m(2)]: enalaprilat, 41.8 +/- 7.4; imidaprilat, 19.0 +/- 7.8; quinaprilat, 8.9 +/- 1.3). The dialyzabilities of the 3 drugs were negatively correlated with their respective protein-binding rates. During hemodialysis, blood pressure did not change significantly in any group. These results suggest that imidapril provides good blood pressure control without a large fluctuation of drug concentration in hypertensive patients undergoing chronic hemodialysis.

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LC-MS determination and bioavailability study of imidapril hydrochloride after the oral administration of imidapril tablets in human volunteers

et al. 2005

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The purpose of the present study was to develop a standard protocol for imidapril hydrochloride bioequivalence testing. For this reason, a specific LC-MS method was developed and validated for the determination of imidapril in human plasma. A solid-phase extraction cartridge, Sep-pak C18, was used to extract imidapril and ramipril (an internal standard) from deproteinized plasma. The compounds were separated using a XTerra MS C18 column (3.5 microm, 2.1 x 150 mm) and acetonitrile-0.1% formic acid (67:33, v/v) adjusted to pH 2.4 by 2 mmol/L ammonium formic acid, as mobile phase at 0.3 mL/min. Imidapril was detected as m/z 406 at a retention time of ca. 2.3 min, and ramipril as m/z 417 at ca. 3.6 min. The described method showed acceptable specificity, linearity from 0.5 to 100 ng/mL, precision (expressed as a relative standard deviation of less than 15%), accuracy, and stability. The plasma concentration-versus-time curves of eight healthy male volunteers administered a single dose of imidapril (10 mg), gave an AUC12hr of imidapril of 121.48 +/- 35.81 ng mL(-1) h, and Cmax and Tmax values of 32.59 +/- 9.76 ng/mL and 1.75 +/- 0.27 h. The developed method should be useful for the determination of imidapril in plasma with sufficient sensitivity and specificity in bioequivalence study.

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Single dose and steady state pharmacokinetics and pharmacodynamics of the ACE‐inhibitor imidapril in hypertensive patients

Cited by 13 publications

References 12 publications

Pharmacodynamic Evaluation of 4 Angiotensin‐Converting Enzyme Inhibitors in Healthy Adult Horses

Pharmacodynamic Evaluation of 4 Angiotensin‐Converting Enzyme Inhibitors in Healthy Adult Horses

Clearance of Imidapril, an Angiotensin‐Converting Enzyme Inhibitor, During Hemodialysis in Hypertensive Renal Failure Patients: Comparison With Quinapril and Enalapril

LC-MS determination and bioavailability study of imidapril hydrochloride after the oral administration of imidapril tablets in human volunteers

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