Tegaserod pharmacokinetics are similar in patients with severe renal insufficiency and in healthy subjects.
Tegaserod (HTF 919), a selective 5-HT4 receptor partial agonist with promotile activity throughout the gastrointestinal tract, is in development for the treatment of irritable bowel syndrome. In an open-label, parallel-group study, the pharmacokinetics of a single 12-mg oral dose of tegaserod in patients with severe renal insufficiency requiring hemodialysis were compared with data obtained from healthy subjects matched for age, weight, height, and gender (n = 10, both). The pharmacokinetics of tegaserod were similar in both groups (AUC(0h-tz), ng.h/ml: 14.6 +/- 8.5 vs. 14.3 +/- 7.1; Cmax, ng/ml: 4.6 +/- 2.3 vs. 5.1 +/- 2.2; tmax, h: 1.0, for both). Tegaserod had similar tolerability in renally impaired patients and healthy volunteers, with adverse events largely related to the gastrointestinal pharmacological actions of the drug. Therefore, no dose adjustment of tegaserod is necessary for patients with renal insufficiency.
Hennepin County Medical Center, Total Renal Research, Inc., Minneapolis, Minnesota, USA.
Suzanne K
SK
Swan
Honghui
H
Zhou
Ann
A
Horowitz
Latifa
L
Alladina
Martine
M
Hubert
Silke
S
Appel-Dingemanse
Stuart
S
Osborne
Larry
L
Lambrecht
James F
JF
McLeod
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000187:drug effects*; D044422:Receptors, Serotonin, 5-HT4; D006435:Renal Dialysis; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013997:Time Factors
D007211:Indoles; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C105050:tegaserod