PMID- 21704241
OWN - NLM
STAT- MEDLINE
DCOM- 20111017
LR  - 20131121
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 33
IP  - 6
DP  - 2011 Jun
TI  - Single-dose bioequivalence of 105-mg fenofibric acid tablets versus 145-mg 
      fenofibrate tablets under fasting and fed conditions: a report of two phase I, 
      open-label, single-dose, randomized, crossover clinical trials.
PG  - 766-75
LID - 10.1016/j.clinthera.2011.05.047 [doi]
AB  - BACKGROUND: Fenofibrate is used to treat primary hypercholesterolemia, mixed 
      lipidemia, and hypertriglyceridemia in adults who do not respond to 
      nonpharmacologic measures. Fenofibrate is a prodrug that is rapidly and 
      completely hydrolyzed to fenofibric acid, the active moiety. A new orally 
      administered agent, fenofibric acid, was developed as an alternative to 
      fenofibrate. OBJECTIVE: Two separate studies were conducted to evaluate the 
      bioequivalence of fenofibric acid relative to fenofibrate under fasted and fed 
      (standard breakfast) conditions, characterize the pharmacokinetic profile, and 
      assess the safety and tolerability of fenofibric acid. METHODS: In study 1 
      (fasted), during each study period, volunteers received a single 105-mg dose of 
      fenofibric acid or single 145-mg dose of fenofibrate (depending on their 
      randomization scheme) after an overnight fast (a minimum fast of 10 hours). A 
      7-day washout period followed the first treatment period, after which the 
      volunteers received the alternate treatment. Study 2 followed a similar dosing 
      scheme and differed only in that volunteers received their single dose after 
      being fed a standard meal (575 calories, of which 36% were contributed by fat). 
      Serial blood samples in both studies were collected up to 72 hours after drug 
      administration. The pharmacokinetic parameters of interest for assessing 
      bioequivalence were AUC(0-t), AUC(0-infinity), C(max), and T(max). The criterion for a 
      lack of difference between products was a 90% CI between 0.80 and 1.25 for the 
      fenofibric acid:fenofibrate ratios for AUC(0-t), AUC(0-infinity), and C(max.) 
      Tolerability was assessed by adverse events (AEs), laboratory parameters, vital 
      signs, and physical examinations. RESULTS: Volunteers in study 1 (fasted; n = 54) 
      were aged 18 to 43 years; 19 (35%) were men and 35 (65%) were women; mean weight 
      was 155.2 pounds (range, 103.0-267.0 pounds); and 48 (89%) were white, 1 (2%) was 
      black, and 5 (9%) were white/American Indian/Alaskan native/Asian. Volunteers in 
      study 2 (fed; n = 54) were aged 18 to 43 years; 27 (50%) were men and 27 (50%) 
      were women; mean weight was 161.9 pounds (range, 112.0-225.0 pounds); and 51 
      (94%) were white (including 2 Hispanic) and 3 (6%) were black. The 90% CIs about 
      the ratio of the fenofibric acid geometric mean to the fenofibrate geometric mean 
      were within the 80% and 125% limits for the pharmacokinetic parameters C(max), 
      AUC(0-t), and AUC(0-infinity) of the ln-transformed data in both study 1 (fasted) and 
      study 2. In study 1 (fasted), 14 volunteers (26%) experienced a total of 29 AEs; 
      the most common nonlaboratory AEs were dizziness (6%) and headache (4%). In study 
      2, 12 volunteers (22%) experienced a total of 19 AEs; the most common 
      nonlaboratory AEs were headache (17%) and dry throat (4%). AEs were generally 
      mild or moderate in intensity. CONCLUSIONS: In these 2 single-dose studies, these 
      healthy volunteers administered a single oral dose of 105-mg fenofibric acid met 
      the US Food and Drug Administration regulatory criteria for assuming 
      bioequivalence to a single oral dose of 145-mg fenofibrate tablets with respect 
      to the rate and extent of fenofibric acid absorption in both fed and fasted 
      states. Fenofibric acid at the dose studied was well tolerated in this 
      population.
CI  - Copyright (c) 2011 Elsevier HS Journals, Inc. All rights reserved.
FAU - Godfrey, Anthony R
AU  - Godfrey AR
AD  - PRACS Institute, Ltd, Fargo, North Dakota, USA.
FAU - Digiacinto, Jennifer
AU  - Digiacinto J
FAU - Davis, Matthew W
AU  - Davis MW
LA  - eng
PT  - Clinical Trial, Phase I
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 (Anticholesteremic Agents)
RN  - 0 (Dietary Fats)
RN  - 0 (Prodrugs)
RN  - 0 (Tablets)
RN  - BGF9MN2HU1 (fenofibric acid)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Anticholesteremic Agents/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Dietary Fats/administration & dosage
MH  - Fasting
MH  - Female
MH  - Fenofibrate/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - *Food-Drug Interactions
MH  - Humans
MH  - Male
MH  - Prodrugs
MH  - Tablets
MH  - Therapeutic Equivalency
MH  - Young Adult
EDAT- 2011/06/28 06:00
MHDA- 2011/10/18 06:00
CRDT- 2011/06/28 06:00
PHST- 2011/05/06 00:00 [accepted]
PHST- 2011/06/28 06:00 [entrez]
PHST- 2011/06/28 06:00 [pubmed]
PHST- 2011/10/18 06:00 [medline]
AID - S0149-2918(11)00283-9 [pii]
AID - 10.1016/j.clinthera.2011.05.047 [doi]
PST - ppublish
SO  - Clin Ther. 2011 Jun;33(6):766-75. doi: 10.1016/j.clinthera.2011.05.047.