Cardiovascular effect of almotriptan in treated hypertensive patients.
OBJECTIVE
Our objective was to investigate the cardiovascular effects of almotriptan, a 5-hydroxytryptamine 1B/1D agonist, in treated patients with hypertension.


METHODS
Twenty patients with hypertension controlled by medication received the following treatments in a randomized, double-blind, crossover design: one placebo tablet, one 12.5-mg almotriptan tablet, and one 25-mg almotriptan tablet. Serial blood samples for analysis of almotriptan were obtained through 24 hours after administration. Serial measurements of supine blood pressure, 12-lead electrocardiograms, and Holter electrocardiographic recordings were also obtained. Plasma almotriptan concentrations were measured with use of a liquid chromatography-tandem mass spectrometry assay. Differences between treatments in pharmacokinetic parameters were assessed with an ANOVA model appropriate for a crossover design. Blood pressure measures and QTc intervals were analyzed for treatment effects with use of a similar model. Analyses were performed on weighted mean and maximal changes from baseline for intervals from 0 to 4 and 0 to 12 hours after administration.


RESULTS
Significant linear effects of dose were observed for the maximal change in diastolic blood pressure and for the maximal and mean changes in systolic blood pressure. These effects were consistent for both the 4- and 12-hour periods after dosing. Mean changes from baseline during the interval from 0 to 4 hours were 1.59 +/- 3.88, 1.85 +/- 5.94, and 4.84 +/- 5.99 mm Hg for systolic pressure and 1.38 +/- 6.95, 6.25 +/- 9.54, and 11.0 +/- 10.6 mm Hg for diastolic pressure for placebo, 12.5 mg almotriptan, and 25 mg almotriptan, respectively. No instances of hypertensive crisis were observed. No QTc interval prolongation was observed.


CONCLUSIONS
Almotriptan has effects on blood pressure in subjects with controlled hypertension that are consistent with those of other members of the pharmalogic class.
Fleishaker
Joseph C
JC
Clinical Pharmacology Unit, Pharmacia, Kalamazoo, MI 49007, USA. joseph.c.fleishaker@pharmacia.com
McEnroe
Janet D
JD
Azie
Nkechi E
NE
Francom
Steven F
SF
Carel
Barbara J
BJ
D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007211:Indoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014363:Tryptamines
D007211:Indoles; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C409045:almotriptan