Comparison of pharmacokinetics of two fenofibrate tablet formulations in healthy human subjects.
BACKGROUND
Fenofibrate is a serum lipid-lowering agent used as an adjunct to diet in patients with hypercholesterolemia and hypertriglyceridemia. The new fenofibrate tablet formulation was developed as a pharmaceutical equivalent to the marketed tablet formulation containing 145 mg.


OBJECTIVE
The objective of this study was to compare the pharmacokinetics and safety of 2 tablet formulations containing 145 mg of fenofibrate (CAS number 49562-28-9) in healthy human subjects.


METHODS
The study was a randomized, 2-treatment, 3-period, 3-sequence, single-dose, 3-way crossover, partial replicate bioequivalence study in healthy human subjects under fasting conditions. Eligible subjects received each treatment in a crossover manner according to the randomization schedule. Replicate dosing was conducted for the reference formulation to determine its intrasubject variability. The predose blood sample was taken within 1 hour before dosing, and serial blood sampling was performed up to 72.0 hours' postdose. The analysis of plasma samples for concentrations of fenofibric acid, the active metabolite of fenofibrate, was conducted by using a validated LC-MS/MS method. Bioequivalence was to be concluded if the 90% CIs as constructed were within the range of 80% to 125% for Cmax, AUC0-t, and AUC0-∞ for fenofibric acid. Subjects were monitored for safety and tolerability throughout the study.


RESULTS
15 healthy human subjects between 18 and 45 years of age and having body mass index between 18.5 and 30 kg/m(2) were recruited into the study. The 90% CIs for the test/reference mean ratios of the ln-transformed pharmacokinetic variables Cmax, AUC0-t, and AUC0-∞ were within the conventional bioequivalence range of 80% to 125%. Both formulations were well tolerated after a single oral dose in these healthy male subjects.


CONCLUSIONS
Both fenofibrate tablet formulations demonstrated equivalent rates and extent of systemic absorption, and hence were considered bioequivalent.
Department of Clinical and Bioequivalence Research, Cipla Limited, Mumbai, India. Electronic address: siddharth.chachad@cipla.com.
Siddharth S
SS
Chachad
Department of Clinical and Bioequivalence Research, Cipla Limited, Mumbai, India.
Milind
M
Gole
Department of Clinical and Bioequivalence Research, Cipla Limited, Mumbai, India.
Geena
G
Malhotra
Contract Research Organisation, Sitec Labs Pvt Ltd, Mumbai, India.
Raghu
R
Naidu
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D011345:Fenofibrate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
D013607:Tablets; C006012:fenofibric acid; D011345:Fenofibrate
bioequivalence; fenofibrate; pharmacokinetics