PMID- 23274144
OWN - NLM
STAT- MEDLINE
DCOM- 20130702
LR  - 20221207
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 35
IP  - 1
DP  - 2013 Jan
TI  - Pharmacokinetic properties of single-dose lamivudine/adefovir dipivoxil 
      fixed-dose combination in healthy Chinese male volunteers.
PG  - 68-76
LID - S0149-2918(12)00658-3 [pii]
LID - 10.1016/j.clinthera.2012.12.001 [doi]
AB  - BACKGROUND: Both lamivudine and adefovir dipivoxil are approved for the treatment 
      of chronic hepatitis B (CHB) and have established safety profiles. A fixed-dose 
      combination (FDC) formulation of lamivudine/adefovir dipivoxil for the treatment 
      of CHB may provide dosing convenience and improve adherence. OBJECTIVE: This 
      study compared the pharmacokinetic profiles of an FDC capsule containing 
      lamivudine/adefovir dipivoxil 100/10 mg and conventional lamivudine 100-mg + 
      adefovir dipivoxil 10-mg tablets to determine bioequivalence. METHODS: This 
      randomized, open-label, single-dose, 2-period crossover study was conducted in 
      healthy male Chinese subjects. The study included a screening visit, 2 treatment 
      sessions, and a follow-up visit. Subjects who met the inclusion/exclusion 
      criteria were assigned to receive, in randomized order, 1 FDC capsule or 1 tablet 
      each of lamivudine and adefovir dipivoxil. After a 7- to 10-day washout period, 
      alternate treatment was given to the subjects during the second treatment 
      session. Blood samples were collected immediately before and after dosing for 48 
      hours for plasma drug concentration measurement. Data on adverse events (AEs) 
      were collected from the start of dosing until the follow-up visit. Tolerability 
      assessments included physical examinations with vital sign measurements and 
      clinical laboratory evaluations throughout the study. RESULTS: Forty subjects 
      were enrolled into the study (mean age, 22.4 years [range, 19-28 years]; weight, 
      63.8 kg [range, 54-78 kg]). The pharmacokinetic profiles of lamivudine and 
      adefovir were similar between the FDC and reference formulations. The geometric 
      mean ratios (GMRs) for lamivudine C(max) and AUC(0-last) were 1.02 (90% CI, 
      0.92-1.12) and 0.99 (90% CI, 0.95-1.04), respectively; adefovir, 0.94 (90% CI, 
      0.89-0.99) and 0.95 (90% CI, 0.91-1.00). A limited number of mild AEs were 
      reported, with no clinically significant changes in vital signs or laboratory 
      results. CONCLUSIONS: The FDC capsule was bioequivalent to the concurrent 
      administration of lamivudine + adefovir dipivoxil tablets based on the 90% CIs of 
      the GMRs for C(max), AUC(0-infinity), AUC(0-last), and t12 (all were between 0.80 and 
      1.25). Both treatments were well-tolerated.
CI  - Copyright (c) 2013 Elsevier HS Journals, Inc. All rights reserved.
FAU - Fok, Benny S P
AU  - Fok BS
AD  - Division of Clinical Pharmacology, Department of Medicine and Therapeutics, The 
      Chinese University of Hong Kong, Shatin, Hong Kong SAR.
FAU - Gardner, Stephen
AU  - Gardner S
FAU - Piscitelli, Steve
AU  - Piscitelli S
FAU - Chen, Shuguang
AU  - Chen S
FAU - Chu, Tanya T W
AU  - Chu TT
FAU - Chan, Jones C M
AU  - Chan JC
FAU - Tomlinson, Brian
AU  - Tomlinson B
LA  - eng
SI  - ClinicalTrials.gov/NCT01353742
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20121228
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antiviral Agents)
RN  - 0 (Capsules)
RN  - 0 (Drug Combinations)
RN  - 0 (Organophosphonates)
RN  - 0 (Tablets)
RN  - 2T8Q726O95 (Lamivudine)
RN  - JAC85A2161 (Adenine)
RN  - U6Q8Z01514 (adefovir dipivoxil)
SB  - IM
MH  - Adenine/administration & dosage/adverse effects/*analogs & 
      derivatives/blood/pharmacokinetics
MH  - Administration, Oral
MH  - Adult
MH  - Antiviral Agents/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Area Under Curve
MH  - Asian People
MH  - Biological Availability
MH  - Capsules
MH  - Cross-Over Studies
MH  - Drug Combinations
MH  - Drug Therapy, Combination
MH  - Half-Life
MH  - Hong Kong
MH  - Humans
MH  - Lamivudine/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Organophosphonates/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Tablets
MH  - Therapeutic Equivalency
MH  - Young Adult
EDAT- 2013/01/01 06:00
MHDA- 2013/07/03 06:00
CRDT- 2013/01/01 06:00
PHST- 2012/09/21 00:00 [received]
PHST- 2012/12/04 00:00 [revised]
PHST- 2012/12/04 00:00 [accepted]
PHST- 2013/01/01 06:00 [entrez]
PHST- 2013/01/01 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
AID - S0149-2918(12)00658-3 [pii]
AID - 10.1016/j.clinthera.2012.12.001 [doi]
PST - ppublish
SO  - Clin Ther. 2013 Jan;35(1):68-76. doi: 10.1016/j.clinthera.2012.12.001. Epub 2012 
      Dec 28.