title: Effect of food on the oral bioavailability of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide fixed dose combination tablets in healthy subjects.
abstract: A double fixed dose combination of amlodipine/valsartan and triple fixed dose combination of amlodipine/valsartan/HCTZ tablets have been developed to treat patients with moderate-to-severe hypertension. Here, we present the effect of food on the oral bioavailability of these two fixed dose combination tablets from two separate clinical studies in healthy subjects. Single oral doses of amlodipine/valsartan (10/160 mg) and amlodipine/valsartan/HCTZ (10/320/25 mg were administered under fasted or fed conditions. Blood samples were collected in both studies to determine the pharmacokinetic parameters of amlodipine, valsartan, and/or HCTZ using non-compartmental analysis. Following amlodipine/valsartan administration, the geometric mean ratios (GMRs, 90% CI) of AUC0-∞ and Cmax were 1.09 (1.05-1.13) and 1.03 (0.97-1.09) for amlodipine, and 0.94 (0.81-1.10) and 0.86 (0.73-1.02) for valsartan, respectively. Following amlodipine/valsartan/HCTZ administration, the GMRs (90%CI) of AUC0-∞ and Cmax were 1.09 (1.04-1.15) and 1.11 (1.05-1.08) for amlodipine, 1.14 (0.99-1.31) and 1.12 (0.98-1.29) for valsartan, and 1.09 (1.02-1.16) and 0.86 (0.79-0.93) for HCTZ, respectively. Considering the sample size and pharmacokinetic variability associated with analytes, these study results indicate that food effect is minimal or none when fixed dose combination tablets are administered with food. In conclusion, both fixed dose combination tablets can be administered without regards to meals.
authors.affiliation: Novartis Institute for Biomedical Research, East Hanover, NJ, USA.
authors.forename: Gangadhar
authors.initials: G
authors.lastname: Sunkara
authors.affiliation: Novartis Institute for Biomedical Research, East Hanover, NJ, USA.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Novartis Institute for Biomedical Research, East Hanover, NJ, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Reynolds
authors.affiliation: Novartis Institute for Biomedical Research, East Hanover, NJ, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Serra
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Novartis Institute for Biomedical Research, East Hanover, NJ, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Ligueros-Saylan
authors.affiliation: Novartis Institute for Biomedical Research, East Hanover, NJ, USA.
authors.forename: Surya
authors.initials: S
authors.lastname: Ayalasomayajula
authors.affiliation: Novartis Pharmaceuticals AG, Basel, Switzerland.
authors.forename: Serge
authors.initials: S
authors.lastname: Winter
authors.affiliation: Novartis Institute for Biomedical Research, East Hanover, NJ, USA.
authors.forename: Venkateswar
authors.initials: V
authors.lastname: Jarugula
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000068838:Amlodipine, Valsartan Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage; D004338:Drug Combinations; D016903:Drug Monitoring; D005260:Female; D018565:Food-Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013607:Tablets; D055815:Young Adult
chemical_list: D000068838:Amlodipine, Valsartan Drug Combination; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004041:Dietary Fats; D004338:Drug Combinations; D013607:Tablets; D006852:Hydrochlorothiazide
keywords: amlodipine; fixed dose combination; food effect; valsartan and hydrochlorothiazide (HCTZ)