[The additional efficacy of the nifedipine-diuretic combination depends on the potency of the drug administered first and not the sequence of administration. A double blind study in salt-sensitive black hypertensives].
OBJECTIVE
To evaluate whether the additional antihypertensive efficacy of the nifedipine-thiazide combination depends on the sequence of drug administration and whether the natriuretic effect of thiazide persists when co-administered with nifedipine.


METHODS
Double blind, randomised, crossover, placebo-controlled study, in 12 salt-sensitive hypertensive black patients (SSH). Evaluation of the antihypertensive (24 h ambulatory monitoring) and natriuretic effects of placebo (PL), of nifedipine-GITS (NIF, 30 mg/d) and of hydrochlorothiazide (HCTZ, 25 mg/d) given alone and in combination within two separate therapeutic sequences: PL-->NIF-->NIF + HCTZ and PL-->HCTZ-->HCTZ + NIF (1 month for each therapeutic regimen).


RESULTS
NIF induced greater (p < 0.04) reduction of 24 h mean arterial pressure (MAP) (-15.9 +/- 1.9 mm Hg, v PL) than HCTZ (-9.0 +/- 1.3 mm Hg). The association of NIF to HCTZ induced a greater (p < 0.05) additional reduction of MAP-24 h (9.7 +/- 2.2 mm Hg) than that produced by the association of HCTZ to NIF (4.1 +/- 1.3 mm Hg). NIF alone and in combination did not modify the diuresis-natriuresis observed with the previous treatment, whereas HCTZ alone and in combination always increased diuresis (by 25%) and natriuresis (by 53%). There was a significant negative correlation (r = -0.71, p < 0.001) between blood pressure (BP) reduction induced by the drug administered first (NIF or HCTZ) and the additional BP reduction obtained by the association of the second drug.


CONCLUSIONS
In most of the SSH the NIF-GITS was more potent than HCTZ. NIF did not modify the diuretic-natriuretic effect of PL and of HCTZ. The greater potency of NIF may explain why in most patients the combination HCTZ to NIF induced a lower hypotensive effect than that of the association of NIF to HCTZ. Independently of the sequence of the drug administration, the lower the hypotensive effect of the drug administered first the greater the additional hypotensive effect that was observed by adding the second drug.
Damasceno
A
A
Faculdade de Medicina da Universidade Eduardo Mondlane, Maputo, Moçambique.
Caupers
P
P
Rafik
A
A
Santos
A
A
Polónia
J
J
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D044383:Black People; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004232:Diuretics; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use*; D012965:Sodium Chloride; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D012965:Sodium Chloride; D009543:Nifedipine