The effect of AST-120 on the single-dose pharmacokinetics of losartan and losartan acid (E-3174) in healthy subjects.

Author(s): Marier JF, Guilbaud R, Kambhampati SR, Mathew P, Moberly J, Lee J, Salazar DE

Affiliation(s): MDS Pharma Services, PK/PD, 2350 Cohen Street, St-Laurent, Montreal, Canada.

Publication date & source: 2006-03, J Clin Pharmacol., 46(3):310-20.

Publication type: Randomized Controlled Trial

AST-120 is an orally administered adsorbent used to slow the progression of chronic kidney disease (CKD). This was a randomized, open-label, 5-way crossover study to assess the effect of AST-120 on the pharmacokinetics of losartan and its active metabolite (E-3174) in healthy subjects. Losartan (100 mg) was administered alone under fasting (A) and fed (B) conditions, and results were compared when AST-120 (3 g thrice daily for 2 days) was administered 60 minutes after (C), 30 minutes prior to (D), and 30 minutes after (E) losartan. Plasma concentrations of losartan and E-3174 were assayed by high-performance liquid chromatography with mass spectrometry detection. Under fed conditions, treatment C had no significant effect on the AUC(0-t) and Cmax of losartan and E-3174. Treatments D and E resulted in a marked decrease in Cmax of losartan and E-3174. Therefore, administration of AST-120 60 minutes after losartan under fed conditions may be preferred over other dosing regimens for CKD patients.