Functional antagonism between PK 11195, a peripheral benzodiazepine receptor antagonist, and nicardipine at the vascular level in healthy subjects: a peripheral hemodynamic study.
The effects of PK 11195, a peripheral benzodiazepine receptor antagonist (200 mg orally), of nicardipine (20 mg orally), of their combination, and of a placebo on brachial and carotid arteries, diameters, and flows were determined and compared over a period of 8 h after drug intake during a double-blind and cross-over study performed on six healthy volunteers. Simultaneously, plasma concentrations of both drugs were measured. PK 11195 significantly increased carotid and more markedly brachial arteries, flows (20 and 39%, respectively), and diameters (4 and 7%, respectively) and decreased forearm vascular resistance. Thus, PK 11195 preferentially affected the resistance vascular beds where it dilated both large arteries and arterioles. The intensity and duration of the peripheral vasodilating effects of PK 11195 were similar to those of nicardipine. Simultaneous administration of PK 11195 and nicardipine abolished almost all the peripheral vasodilating effects of both drugs. This finding, which was not related to a pharmacokinetic interaction between PK 11195 and nicardipine, demonstrates that in humans a functional antagonism develops between these two drugs at the vascular level.
Thuillez
C
C
Service de Pharmacologie Clinique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Loueslati
H
H
Duhazé
P
P
Giudicelli
J F
JF
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000502:physiology; D002339:Carotid Arteries / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007546:Isoquinolines / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D009529:Nicardipine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects*; D012083:Renin / Q000097:blood; D013997:Time Factors
D007546:Isoquinolines; D011963:Receptors, GABA-A; D009529:Nicardipine; D012083:Renin; C037850:PK 11195