PMID- 20678685
OWN - NLM
STAT- MEDLINE
DCOM- 20101122
LR  - 20221207
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 32
IP  - 7
DP  - 2010 Jul
TI  - Pharmacokinetics and bioequivalence evaluation of two losartan potassium 50-mg 
      tablets: A single-dose, randomized-sequence, open-label, two-way crossover study 
      in healthy Chinese male volunteers.
PG  - 1387-95
LID - 10.1016/j.clinthera.2010.06.018 [doi]
AB  - BACKGROUND: Losartan is a nonpeptide angiotensin II receptor antagonist used as 
      an antihypertensive agent. The relative bioavailability of a newly developed 
      tablet compared with an established branded formulation has not been reported in 
      a Chinese population. OBJECTIVE: To meet the requirements for marketing a new 
      generic product, the study was designed to compare the pharmacokinetic parameters 
      and relative bioavailability of a new generic losartan potassium 50-mg tablet 
      (test formulation) with a branded 50-mg tablet (reference formulation) in healthy 
      Chinese male volunteers. METHODS: A single-dose, randomized-sequence, openlabel, 
      2-way crossover study was conducted in healthy Chinese male volunteers. Eligible 
      participants were randomly assigned in a 1:1 ratio to receive a single 50-mg 
      tablet of the test or reference formulation, followed by a 1-week washout period 
      and then administration of the alternate formulation. The study drugs were 
      administered after a 10-hour overnight fast. Plasma samples were collected over 
      36 hours. Tolerability was evaluated by recording adverse events (AEs) and 
      monitoring vital signs, ECGs, and laboratory tests at baseline and at completion 
      of the study. Plasma concentrations of losartan and its active metabolite 
      (EXP3174) were analyzed by LC-MS/MS. Pharmacokinetic parameters, including 
      C(max), AUC(0-36), and AUC(0-infinity), were calculated. If the 90% CIs for the 
      log-transformed values of AUC were within 80% to 125%, and that of C(max) was 
      within 70% to 143%, the 2 products would be considered bioequivalent according to 
      the guidelines of the US Food and Drug Administration and the State Food and Drug 
      Administration of China. RESULTS: Twenty-seven healthy Chinese male volunteers 
      participated in this study (mean [SD] age, 24.5 [2.3] years [range, 20-29 years]; 
      weight, 64.6 [4.0] kg [range, 60.0-75.0 kg]; height, 172.2 [4.8] cm [range, 
      165.0183.0 cm]; and body mass index, 21.8 [1.2] kg/m(2) [range, 20.0-25.0 
      kg/m(2)]). One volunteer (3.7%) experienced an AE (microscopic hematuria) after 
      administration of the test formulation. This resolved spontaneously after 10 days 
      and was considered by the investigator as mild; the relationship with the study 
      drug was uncertain. No serious AEs were reported. Both formulations were 
      associated with significant reductions in systolic and diastolic blood pressure 
      and significant increases in heart rate compared with baseline values (all, P < 
      0.05). No period, formulation, or sequence effects were observed for any 
      pharmacokinetic parameter, except for a significant subject effect. For parent 
      losartan, the 90% CIs for the ratios (test/reference) of C(max), AUC(0-36), and 
      AUCAUC(0-infinity) were 83.65% to 113.36%, 89.79% to 98.25%, and 90.95% to 
      99.55%, respectively. For the metabolite EXP3174, the 90% CIs for the ratios of 
      C(max), AUC(0-36), and AUCAUC(0-infinity) were 93.49% to 103.61%, 96.79% to 
      104.09%, and 97.06% to 105.83%. Both C(max) and AUC met the predetermined 
      criteria for assuming bioequivalence. The relative bioavailability of the test 
      formulation to the reference formulation was 93.92% for losartan and 100.40% for 
      EXP3174. CONCLUSIONS: In this small study in healthy Chinese male volunteers, a 
      single 50-mg oral dose of a losartan potassium tablet (test formulation) met the 
      regulatory criteria for assuming bioequivalence to the established reference 
      formulation. Both formulations were well tolerated.
CI  - 2010 Excerpta Medica Inc. All rights reserved.
FAU - Jia, Jing-Ying
AU  - Jia JY
AD  - Shanghai Xuhui Central Hospital, People's Republic of China.
FAU - Zhang, Meng-Qi
AU  - Zhang MQ
FAU - Liu, Yan-Mei
AU  - Liu YM
FAU - Liu, Yun
AU  - Liu Y
FAU - Liu, Gang-Yi
AU  - Liu GY
FAU - Li, Shui-Jun
AU  - Li SJ
FAU - Lu, Chuan
AU  - Lu C
FAU - Weng, Li-ping
AU  - Weng LP
FAU - Qi, Yu-Lin
AU  - Qi YL
FAU - Yu, Chen
AU  - Yu C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Drugs, Generic)
RN  - 0 (Tablets)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Angiotensin II Type 1 Receptor Blockers/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Asian People
MH  - Biological Availability
MH  - China
MH  - Cross-Over Studies
MH  - Drugs, Generic/administration & dosage/adverse effects/*pharmacokinetics
MH  - Humans
MH  - Losartan/administration & dosage/adverse effects/*pharmacokinetics
MH  - Male
MH  - Tablets
MH  - Therapeutic Equivalency
MH  - Young Adult
EDAT- 2010/08/04 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/08/04 06:00
PHST- 2010/05/12 00:00 [accepted]
PHST- 2010/08/04 06:00 [entrez]
PHST- 2010/08/04 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - S0149-2918(10)00209-2 [pii]
AID - 10.1016/j.clinthera.2010.06.018 [doi]
PST - ppublish
SO  - Clin Ther. 2010 Jul;32(7):1387-95. doi: 10.1016/j.clinthera.2010.06.018.