PMID- 15220015
OWN - NLM
STAT- MEDLINE
DCOM- 20040903
LR  - 20221207
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 26
IP  - 5
DP  - 2004 May
TI  - Randomized, open-label, two-period crossover comparison of the pharmacokinetic 
      and pharmacodynamic properties of two amlodipine formulations in healthy adult 
      male Korean subjects.
PG  - 715-23
AB  - BACKGROUND: Amlodipine, a third-generation dihydropyridine calcium antagonist, is 
      prescribed in the management of angina and hypertension. A newly developed 
      amlodipine formulation (amlodipine camsylate) is associated with similar physical 
      properties, melting point, and solubility-and improved stability against 
      long-term stability test and accelerated temperature test-compared with the 
      conventional formulation (amlodipine besylate). OBJECTIVE: This study was 
      performed to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties 
      and safety profiles of a newly developed amlodipine formulation with a 
      conventional formulation in healthy male subjects. METHODS: This randomized, 
      open-label, 2-period crossover comparative study was conducted at the Clinical 
      Trial Center, Gil Medical Center, Gachon Medical School (Incheon, Korea). 
      Eighteen healthy male Korean subjects aged 20 to 40 years were enrolled. All 
      subjects received a single oral dose (5-mg tablet) of a conventional (reference) 
      or newly developed (test) amlodipine formulation. Blood samples for PK analysis 
      of amlodipine were obtained during the 144-hour period after dosing. Systolic and 
      diastolic blood pressure (BP) (SBP and DBP, respectively) and pulse rate (PR) 
      were measured just before each blood sampling. Assessment of safety profiles, 
      including hematology and biochemistry, electrocardiography, urinalysis, and 
      monitoring of adverse events (AEs), was performed. RESULTS: All participants 
      completed both treatment periods. Their mean (SD) age was 22.3 (1.5) years 
      (range, 20-25 years) and their mean (SD) body weight was 67.9 (5.6) kg (range, 
      57-77 kg). The plasma concentration-time profiles of amlodipine were similar 
      after administration of the 2 formulations. The reference and test formulations 
      were pharmacokinetically equivalent. The 90% CIs for the mean treatment ratios of 
      the log-transformed peak plasma concentration and the area under the plasma 
      concentration-time curve were within the predetermined equivalence range of 80% 
      to 125%. Despite administration of a single dose, significant maximal changes in 
      SBP, DBP, and PR were achieved after drug administration for both formulations 
      compared with baseline values (all, P < 0.001). No significant differences in PD 
      profiles were found between the 2 formulations. No clinically relevant changes 
      were observed in physical, biochemical, hematologic, electrocardiographic, or 
      urinalysis findings during the study. Neither formulation caused any AEs during 
      the study. CONCLUSIONS: The 2 amlodipine formulations were pharmacokinetically 
      equivalent and showed similar PD characteristics in these healthy male subjects.
FAU - Park, Ji-Young
AU  - Park JY
AD  - Department of Pharmacology, Clinical Trial Center, Gil Medical Center, Gachon 
      Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, Korea. 
      jypark@gachon.ac.kr
FAU - Kim, Kyoung-Ah
AU  - Kim KA
FAU - Lee, Gwan-Sun
AU  - Lee GS
FAU - Park, Pil-Whan
AU  - Park PW
FAU - Kim, Su-Lyun
AU  - Kim SL
FAU - Lee, Young-Suk
AU  - Lee YS
FAU - Lee, Young-Wook
AU  - Lee YW
FAU - Shin, Eak-Kyun
AU  - Shin EK
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antihypertensive Agents)
RN  - 1J444QC288 (Amlodipine)
SB  - IM
MH  - Adult
MH  - Amlodipine/administration & dosage/*pharmacokinetics/*pharmacology
MH  - Antihypertensive Agents/administration & dosage/*pharmacokinetics/*pharmacology
MH  - Area Under Curve
MH  - Asian People
MH  - Biological Availability
MH  - Cross-Over Studies
MH  - Half-Life
MH  - Humans
MH  - Male
EDAT- 2004/06/29 05:00
MHDA- 2004/09/04 05:00
CRDT- 2004/06/29 05:00
PHST- 2004/03/04 00:00 [accepted]
PHST- 2004/06/29 05:00 [pubmed]
PHST- 2004/09/04 05:00 [medline]
PHST- 2004/06/29 05:00 [entrez]
AID - S0149291804900719 [pii]
AID - 10.1016/s0149-2918(04)90071-9 [doi]
PST - ppublish
SO  - Clin Ther. 2004 May;26(5):715-23. doi: 10.1016/s0149-2918(04)90071-9.