47226
document
The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects . The pharmacodynamic effects and acceptability of perindopril ( 4 mg daily ) and hydrochlorothiazide ( 25 mg daily ) given alone or in combination for 1 month were investigated in a double-blind , placebo controlled , parallel group study . The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups . Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide ( 11/7 mm Hg supine ) given alone at these doses . The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure ( 24.5/12.6 mm Hg supine ) taking into account the placebo response . The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide . The formation of perindoprilat was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group . Perindopril , whether given alone or in combination with hydrochlorothiazide , was well tolerated and produced no clinically significant change in routine haematology or serum biochemistry . The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction .
47227
Intervention_Pharmacological
perindopril
47228
Intervention_Pharmacological
hydrochlorothiazide
47229
Intervention_Pharmacological
perindopril
47230
Intervention_Pharmacological
hydrochlorothiazide
47231
Intervention_Control
placebo
47232
Intervention_Pharmacological
perindopril
47233
Intervention_Pharmacological
perindopril
47234
Intervention_Pharmacological
hydrochlorothiazide
47235
Intervention_Pharmacological
perindopril
47236
Intervention_Pharmacological
hydrochlorothiazide
47237
Intervention_Pharmacological
perindoprilat
47238
Intervention_Pharmacological
hydrochlorothiazide
47239
Intervention_Pharmacological
Perindopril
47240
Intervention_Pharmacological
hydrochlorothiazide
47241
Intervention_Pharmacological
perindopril
47242
Intervention_Pharmacological
hydrochlorothiazide
47243
Outcome_Other
effect
47244
Outcome_Physical
pharmacodynamic effects
47245
Outcome_Other
pharmacokinetics
47246
Outcome_Physical
time course of angiotensin converting enzyme inhibition
47247
Outcome_Physical
blood pressure
47248
Outcome_Physical
diastolic blood pressure
47249
Outcome_Physical
systolic blood pressure
47250
Outcome_Physical
plasma renin activity
47251
Outcome_Physical
perindoprilat
47252
Outcome_Physical
ACE inhibition
47253
Outcome_Other
well tolerated
47254
Outcome_Physical
routine haematology or serum biochemistry
47255
Participant_Condition
hypertensive
47256
Participant_Sample-size
two