Effect of Hydrochlorothiazide on the Pharmacokinetics of Enalapril in Hypertensive Patients with Varying Renal Function

Hersh, A.D.; Kelly, John G.; Laher, M; Carmody, M.; Doyle, Gerald D.

doi:10.1097/00005344-199601000-00002

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…A similar finding was reported by Hersh et al. , who compared enalapril pharmacokinetics and blood pressure response in hypertensive patients with no, mild or moderate renal impairment [14].…”

Section: Discussionsupporting

confidence: 85%

Blood pressure response to conventional and low‐dose enalapril in chronic renal failure

Elung-Jensen

Heisterberg

Kamper

et al. 2003

Brit J Clinical Pharma

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AimsIn chronic renal failure, the clearance of most ACE inhibitors including enalapril is reduced. Hence, with conventional dosage, plasma enalaprilat may be markedly elevated. It is unclear whether this excess of drug exposure affords an improved control of blood pressure. The aim of the present study was to evaluate short-term blood pressure response to two different plasma levels of enalaprilat. Methods As part of an open, randomized, controlled trial of the effect of high and low dosage of enalapril on the progression of renal failure, short-term blood pressure response was evaluated. Data were analysed in all patients completing 3 months of follow-up. The patients were allocated to two trough plasma concentrations of enalaprilat, either above 50 ng ml -1 (high) ( n = 17) or below 10 ng ml -1 (low) ( n = 18), and the daily dose of enalapril titrated accordingly. Results Median (range) glomerular filtration rate (GFR) at baseline was 18 (7.9) in the high enalaprilat concentration group and 17 (7.3) ml min -1 1.73 m 2 in the low concentration group (NS). Nine patients in each group were on treatment with enalapril at baseline with a median daily dose of 5 mg in both the high (5-10) and low (2.5-20) concentration group. At 3 months' follow-up, the dose was 10 (2.5-30) and 1.9 (1.25-5) mg ( P < 0.0001), respectively. After 3 months median trough concentrations of enalaprilat were 82.5 (22-244) ng ml -1 and 9.1 (2.5-74.8) ng ml -1 ( P < 0.002). At baseline the median systolic blood pressures in the two groups were 140 (110-200) and 133 (110-165), in the high and low enalaprilat concentration groups, respectively, and after 3 months they were 135 (105-170) and 130 (105-170) mmHg (NS). Median diastolic blood pressure was 80 mmHg in each group both at baseline (65-100) and at follow-up (60-95) (NS). There was no difference between the groups in concomitant antihypertensive treatment (number of patients treated, mean daily dose) during the observation period. Proteinuria remained stable during the study period in both groups; patients in the high concentration group had higher plasma potassium concentrations at day 90 and patients in the low group experienced a slight increase in GFR. Conclusions In moderate to severe chronic renal insufficiency the same degree of blood pressure control was achieved on low as well as moderate daily doses of enalapril. This was irrespective of concomitant antihypertensive treatment.

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Section: Discussionsupporting

confidence: 85%

Blood pressure response to conventional and low‐dose enalapril in chronic renal failure

Elung-Jensen

Heisterberg

Kamper

et al. 2003

Brit J Clinical Pharma

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“…This administration and at 1 and 2 h following administration. Otherwise subjects were fasting from 8 h before until 4 h result was also found in one study with enalapril/HCTZ [7], but, in another study, the level of enalaprilat achieved after drug administration. Blood samples for determination of fosinoprilat and HCTZ concentration and for ACE was increased significantly when enalapril was administered following HCTZ independent of the degree of activity and cumulative urine collections were obtained before and up to 24 h (day 1) or 48 h (day 5) after renal impairment [8].…”

supporting

confidence: 52%

“…and a decrease in urinary elimination at lower rates of GFR which correlated predictably with the degree of The pharmacokinetic results showed there were no clinically significant differences between the renally renal impairment [7]. Another study, however, found that the administration of enalapril with HCTZ was impaired patients and the normal subjects.…”

mentioning

confidence: 85%

“…Fixed combinations of an ACEI and HCTZ have been This study was designed to investigate the pharmacokinetics of fosinoprilat in the presence of HCTZ in studied previously [5][6][7][8]. The coadministration of lisinopril and HCTZ showed no pharmacokinetic internormal subjects and renally impaired patients and was carried out in the fasted state to avoid reductions in action in a study of normal subjects [6].…”

mentioning

confidence: 99%

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Fosinopril/hydrochlorothiazide: single dose and steady‐state pharmacokinetics and pharmacodynamics

O'Grady

Yee

Lins

et al. 1999

Brit J Clinical Pharma

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Aims Fosinoprilat, the active product of fosinopril, is eliminated by an hepatic pathway in addition to the renal pathway shared by other angiotensin converting enzyme inhibitors (ACEIs). This study aimed to determine whether impaired renal function affects the pharmacokinetics and pharmacodynamics of a combination of fosinopril and hydrochlorothiazide (HCTZ). Methods The study had a parallel-group design comparing patients with renal impairment and body-mass-index-matched normal controls. The study was done in a University clinic in 13 patients with renal impairment (mean creatinine clearance 55.7±15.6 ml min −1 1.73 m −2 ) and 13 age-, sex-, and body-mass-index-matched normal controls (mean creatinine clearance 102.4±8.9 ml min −1 1.73 m −2 ). All patients and normal controls received fosinopril sodium 20 mg and HCTZ 12.5 mg as a daily oral administration on days 1-5. Non-compartmental pharmacokinetic parameters of fosinoprilat and HCTZ were determined from blood and urine samples obtained over 48 h starting on Day 1 (single dose) and Day 5 (steady state): maximum serum concentration (C max ), time to maximum serum concentration (t max ), area under the serum concentration-time curve during the dosing interval (AUC), cumulative urinary excretion (CUE) and the accumulation index (AI; ratio of AUC-day 5/AUC-day 1). Pharmacodynamic parameters were also measured over 24 h on day 1 and over 48 h on day 5: serum ACE activity and arterial blood pressure. P=0.29). In both groups ACE inhibition and blood pressure response were similar over 24 h and slightly greater 48 h after last dosing. Conclusions In renally impaired subjects fosinopril and HCTZ can be coadministered without undue increases in fosinoprilat concentrations or any clinically significant pharmacodynamic effects. This is probably due to the dual excretory pathways for fosinoprilat.

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Enalapril dosage in progressive chronic nephropathy: a randomised, controlled trial

Elung-Jensen

Heisterberg

Sonne

et al. 2005

Eur J Clin Pharmacol

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In patients with moderate to severe renal insufficiency, a low concentration of enalaprilat afforded the same degree of renoprotection, blood pressure control and minimisation of proteinuria as a high concentration, during 12 months of follow-up. The high-dosage treatment was associated with a more pronounced tendency to hyperkalaemia. Thus, there seems to be no indication for increasing the daily dose of enalapril beyond what achieves adequate blood pressure control in this group of patients.

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Effect of Hydrochlorothiazide on the Pharmacokinetics of Enalapril in Hypertensive Patients with Varying Renal Function

Cited by 5 publications

References 13 publications

Blood pressure response to conventional and low‐dose enalapril in chronic renal failure

Blood pressure response to conventional and low‐dose enalapril in chronic renal failure

Fosinopril/hydrochlorothiazide: single dose and steady‐state pharmacokinetics and pharmacodynamics

Enalapril dosage in progressive chronic nephropathy: a randomised, controlled trial

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