Lack of a pharmacokinetic interaction between moexipril and hydrochlorothiazide.
OBJECTIVE
To investigate the potential for pharmacokinetic interactions between moexipril, a new converting enzyme inhibitor, and hydrochlorothiazide after single dose administration.


METHODS
12 healthy male volunteers were studied by an open, randomised, three-way cross-over design, in which single doses of moexipril, hydrochlorothiazide and the two drugs together were administered. Blood and urine were collected up to 48 hours for measurement of the concentrations of moexipril and its metabolite moexiprilat. In addition, the urine samples were analysed for hydrochlorothiazide.


RESULTS
For the area under the plasma concentration-time curve calculated from time 0 to a concentration greater than zero, AUC(O-t), the study showed a mean value of moexipril 437 ng.ml-1.h-1 following administration of moexipril alone and 416 ng.ml-1.h-1 following moexipril concomitantly with hydrochlorothiazide. The corresponding values for the metabolite moexiprilat were 203 and 215 ng.ml-1.h-1, respectively. The Cmax of moexipril and the metabolite (data of the metabolite in parenthesis) were 245.4 (70.8) ng.ml-1 after administration of moexipril alone and 241.0 (69.2) ng.ml-1 after coadministration of hydrochlorothiazide. The mean total renal excretion (TUE) of hydrochlorothiazide was 15.2 mg when administered alone and 15.1 mg when given together with moexipril. The corresponding mean TUE-values for moexiprilat were 334 (1200) and 453 (1460) micrograms.


CONCLUSIONS
The coadministration of moexipril with hydrochlorothiazide had no demonstrable effect on the measured pharmacokinetic parameters of moexipril, its active metabolite moexiprilat or hydrochlorothiazide.
Hutt
V
V
LAB Gesellschaft für Pharmakologische Untersuchungen mbH and Co, Neu-Ulm, Germany.
Michaelis
K
K
Verbesselt
R
R
De Schepper
P J
PJ
Salomon
P
P
Bonn
R
R
Cawello
W
W
Angehrn
J C
JC
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D004232:Diuretics; D004347:Drug Interactions; D006801:Humans; D006852:Hydrochlorothiazide / Q000493:pharmacokinetics*; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008297:Male; D049993:Sodium Chloride Symporter Inhibitors / Q000493:pharmacokinetics*; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D007546:Isoquinolines; D049993:Sodium Chloride Symporter Inhibitors; D044005:Tetrahydroisoquinolines; D006852:Hydrochlorothiazide; C059506:moexiprilat; C058302:moexipril