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 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.
MDS Pharma Services, PK/PD, 2350 Cohen Street, St-Laurent, Montreal, Canada.
Jean-Francois
JF
Marier
Rudolf
R
Guilbaud
Siva Rama Prasad
SR
Kambhampati
Philip
P
Mathew
James
J
Moberly
James
J
Lee
Daniel E
DE
Salazar
D000327:Adsorption; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000097:blood / Q000493:pharmacokinetics*; D002244:Carbon / Q000494:pharmacology*; D018592:Cross-Over Studies; D004041:Dietary Fats; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D018565:Food-Drug Interactions; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics*; D019808:Losartan / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010087:Oxides / Q000494:pharmacology*; D013777:Tetrazoles / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D004041:Dietary Fats; D005765:Gastrointestinal Agents; D007093:Imidazoles; D010087:Oxides; D013777:Tetrazoles; D002244:Carbon; C040896:AST 120; C066026:losartan carboxylic acid; D019808:Losartan