The Effect of AST‐120 on the Single‐Dose Pharmacokinetics of Losartan and Losartan Acid (E‐3174) in Healthy Subjects

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 Cmaxof losartan and E‐3174. Treatments D and E resulted in a marked decrease in Cmaxof 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.