Pharmacokinetics and biological effects of captopril and hydrochlorothiazide after acute and chronic administration either alone or in combination in hypertensive patients
| Autor: | JF Giudicelli, A Mattei, C Richer |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Adult
Male medicine.medical_specialty Captopril Pharmacology Peptidyl-Dipeptidase A Essential hypertension Plasma renin activity Normal renal function Random Allocation Hydrochlorothiazide Pharmacokinetics Internal medicine Renin–angiotensin system Renin medicine Humans Pharmacology (medical) Dosing cardiovascular diseases business.industry Articles Middle Aged medicine.disease Drug Combinations Kinetics Endocrinology Hypertension Female business hormones hormone substitutes and hormone antagonists medicine.drug circulatory and respiratory physiology |
| Zdroj: | British journal of clinical pharmacology. 23 |
| ISSN: | 0306-5251 |
| Popis: | The pharmacokinetics of free unchanged captopril, total captopril and hydrochlorothiazide (HCTZ) were investigated in three groups of patients with moderate essential hypertension and normal renal function on the first and on the 45th days of an oral treatment with either captopril (50 mg once daily, n = 7) or HCTZ (25 mg once daily, n = 10) or their combination captopril 50 mg + HCTZ 25 mg once daily, n = 8. Simultaneously, the effects of the three treatments on plasma converting enzyme activity (PCEA) and plasma renin activity (PRA) were measured. Elimination half-lives of total captopril after acute (7.8 +/- 2.3 h) or chronic (7.0 +/- 0.5 h) captopril dosing were similar to those of HCTZ after acute (6.5 +/- 1.0 h) or chronic (8.0 +/- 2.5 h) HCTZ dosing. Elimination half-life of free unchanged captopril was 0.81 +/- 0.09 h after acute and 0.96 +/- 0.03 h after chronic captopril dosing. Addition of HCTZ to captopril induced no major change in free and total captopril pharmacokinetic parameters, in PCEA inhibition and in PRA increase (as they were determined after captopril alone) on acute as well as on chronic treatment. Addition of captopril to HCTZ induced no major change in HCTZ pharmacokinetic parameters and in PRA increase compared with those determined after HCTZ alone. Chronic treatment with captopril + HCTZ resulted, like chronic captopril treatment, in no accumulation of captopril, in no significant modification of free and total captopril pharmacokinetic parameters and of PCEA inhibition (as determined after acute administration) but led to a significant enhancement of the acutely induced increase in PRA. Chronic treatment with captopril + HCTZ resulted, like chronic HCTZ treatment, in no accumulation of HCTZ, in no significant modification of HCTZ pharmacokinetic parameters (as determined after acute administration) but also led to a significant enhancement of the acutely induced increase in PRA. Thus, the longer duration of the antihypertensive action of captopril + HCTZ as compared to that of captopril cannot be ascribed to a pharmacokinetic or biological interaction between captopril and HCTZ. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text