Sevelamer hydrochloride (Renagel), a phosphate-binding polymer, does not alter the pharmacokinetics of two commonly used antihypertensives in healthy volunteers.
Sevelamer hydrochloride (Renagel) is a nonabsorbed phosphate-binding polymer approved for the treatment of hyperphosphatemia in adult hemodialysis patients. The authors studied the potential effect of sevelamer on the pharmacokinetics of two antihypertensive drugs, enalapril (20 mg) and metoprolol (100 mg), commonly used in end-stage renal disease patients. Two studies were conducted. Both were single dose, crossover design with or without a 2.4 g dose of sevelamer in healthy volunteers. Within each study, there was a 7-day washout interval between the two dose administrations. There were 28 volunteers in the enalapril study and 32 in the metoprolol study. The mean plasma concentrations versus time profiles of enalapril, enalaprilat, and metoprolol were not altered by the simultaneous administration of sevelamer. Values for the ratio of ln[AUC(0-infinity)], ln[AUC(0-t)], and ln(Cmax] with and without sevelamer were approximately 100%, and the 90% confidence intervals for the ratios of these parameters with and without sevelamer were within the 80% to 125% range in all cases except for the ln[Cmax] of enalapril, which had an upper confidence bound of 125.4%. The authors conclude that sevelamer does not interfere with the absorption and elimination of enalapril and metoprolol.
Burke
S K
SK
GelTex Pharmaceuticals, Inc., 153 Second Avenue, Waltham, MA 02451, USA.
Amin
N S
NS
Incerti
C
C
Plone
M A
MA
Lee
J W
JW
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D004656:Enalapril / Q000097:blood / Q000493:pharmacokinetics*; D004852:Epoxy Compounds / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D010710:Phosphates / Q000378:metabolism; D011073:Polyamines; D011095:Polyethylenes / Q000494:pharmacology*; D000069603:Sevelamer
D000959:Antihypertensive Agents; D004852:Epoxy Compounds; D010710:Phosphates; D011073:Polyamines; D011095:Polyethylenes; D004656:Enalapril; D000069603:Sevelamer; D008790:Metoprolol