The pharmacokinetics of the novel promotile drug, tegaserod, are similar in healthy subjects-male and female, elderly and young.
BACKGROUND
Tegaserod (HTF 919) is a selective 5-HT4 receptor partial agonist in development for the treatment of irritable bowel syndrome.


OBJECTIVE
This study aimed to assess the effect of age and gender on the single-dose pharmacokinetics of tegaserod.


METHODS
In a parallel-group, open-label study, a single dose of tegaserod (12 mg) was administered to four groups of healthy young male, young female, elderly male and elderly female subjects (n=10 per group). Blood samples were collected from 0 to 24 h postdose. Non-compartmental pharmacokinetics evaluation and statistical analysis (ANOVA and Wilcoxon signed ranks test for tmax) were performed.


RESULTS
Tegaserod was well tolerated in all groups. There was no effect of age or gender on tmax and Cmax. Gender did not affect AUC0-infinity and AUC0-tz; there was a statistically significant effect of age on these parameters. AUC0-infinity and AUC0-tz in the elderly were greater than in the young (AUC0-infinity ratio 1.37, P < 0.001; AUC0-tz ratio 1.23, P=0.029). This increase in exposure is judged not to be clinically relevant because it is within the variability in the pharmacokinetics parameters of tegaserod and because the dose-response relationship of tegaserod is relatively shallow.


CONCLUSIONS
No dose adjustment for age or gender is recommended in tegaserod therapy.
Appel-Dingemanse
S
S
Novartis Pharma AG, Basel, Switzerland. silke.appeldingemanse@pharma.novartis.com
Horowitz
A
A
Campestrini
J
J
Osborne
S
S
McLeod
J
J
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000188:drug therapy; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics; D008297:Male; D010528:Peristalsis / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012737:Sex Factors
D007211:Indoles; D017366:Serotonin Receptor Agonists; C105050:tegaserod