title: Pharmacokinetic comparison of amlodipine adipate/valsartan fixed-dose combination with amlodipine besylate/valsartan fixed-dose combination in healthy volunteers.
abstract: The aim of this study was to compare pharmacokinetic characteristics of fixed-dose combination (FDC) of two different salt form of amlodipine, amlodipine adipate/valsartan and amlodipine besylate/ valsartan, in healthy Korean volunteers under fasting conditions. A randomized, open-label, single-dose, two-treatment, two-way crossover study with a 14-day wash-out period was conducted. Plasma samples were collected for up to 144 hours for amlodipine and 24 hours for valsartan. Plasma concentrations of amlodipine and valsartan were analyzed using a validated ultra-performance liquid chromatography tandem mass-spectrometry. A non-compartmental method was used to calculate pharmacokinetic parameters. Vital signs and adverse events were monitored and physical examinations, laboratory tests, and electrocardiograms were conducted to evaluate safety. 44 subjects completed the study. The 90% CIs for the geometric mean ratio of Cmax and the AUC0-t were 93.5 - 100.4% and 93.2 - 98.3% for amlodipine, and 92.1 - 121.3% and 94.1 - 115.2% for valsartan, respectively. 17 adverse events occurred in 15 subjects during the study; 5 and 7 adverse drug reactions from the 5 and 6 subjects were considered to probably be related to the test and reference treatments respectively. All adverse drug reactions were in line with those known for the reference drug. All subjects recovered fully with no sequelae. A FDC of amlodipine adipate/valsartan and amlodipine besylate/valsartan combination tablets met the regulatory criteria for bioequivalence. In addition, no significant difference was observed in the safety assessments between two treatments. Thus, the newly developed FDC of amlodipine adipate/valsartan seems to be interchangeable with amlodipine besylate valsartan combination.
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Nam
authors.forename: Minkyung
authors.initials: M
authors.lastname: Oh
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung Kyun
authors.initials: SK
authors.lastname: Han
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.forename: Geun Seog
authors.initials: GS
authors.lastname: Song
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
authors.forename: Jong-Lyul
authors.initials: JL
authors.lastname: Ghim
authors.forename: Ho-Sook
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000068838:Amlodipine, Valsartan Drug Combination; 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; D044466:Asian People; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004338:Drug Combinations; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008955:Models, Cardiovascular; D056910:Republic of Korea; D053719:Tandem Mass Spectrometry; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000068838:Amlodipine, Valsartan Drug Combination; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D013777:Tetrazoles; D017311:Amlodipine