Evaluation of a pharmacokinetic interaction between valsartan and simvastatin in healthy subjects

Abstract

Based on the wide therapeutic dosage ranges of valsartan and simvastatin, and the highly variable pharmacokinetics of three analytes, the observed differences in the exposure and C(max) of valsartan, simvastatin beta-hydroxy acid and simvastatin in the combination treatment are unlikely to be of clinical relevance.

Assessment of Drug–Drug Interaction Potential Between Atorvastatin and LCZ696, A Novel Angiotensin Receptor Neprilysin Inhibitor, in Healthy Chinese Male Subjects

“…Therefore, sacubitril is less likely to impact any clearance pathways of atorvastatin (both enzyme and transporter mediated). Further, valsartan is recommended is to be administered with statins without any dose adjustments as no pharmacokinetic interaction was observed in a previous clinical study [30].…”

“…The AUC s,ss and C max,ss of valsartan decreased marginally by 9 and 19 %, respectively, when LCZ696 was co-administered with atorvastatin. However, this decrease in the exposure of valsartan is not considered to be clinically significant due to the wide therapeutic range of valsartan and the high inter-subject variability of [50 % associated with its pharmacokinetics [29,30]. Furthermore, although food significantly decreased exposure and C max of valsartan by approximately 40 and 50 %, respectively, food did not affect the pharmacodynamics of valsartan resulting in the recommendation that valsartan can be administered without regards to the meal [31].…”

Use of Mechanistic Modeling to Assess Interindividual Variability and Interspecies Differences in Active Uptake in Human and Rat Hepatocytes

“…At low concentrations, the passive diffusion had limited contribution to the overall uptake for all drugs investigated (Fig. 2), which is of relevance because the unbound C max (after a therapeutic dose) of the drugs studied ranges from 0.80 nM to 0.52 M for pitavastatin and valsartan, respectively (Sunkara et al, 2007;Deng et al, 2008). However, because these drugs are administered orally, concentrations in the hepatic portal vein could be higher and the contribution of passive processes may differ.…”

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…In rats, valsartan did not interfere with the pharmacokinetics of indapamide (Yan et al, 2012). Upon coadministration of valsartan and simvastatin the plasma concentrations of both drugs and the b-hydroxy metabolite of simvastatin are increased by about 20% (Sunkara et al, 2007).…”