Effect of omega-3-acid ethyl esters on steady-state plasma pharmacokinetics of atorvastatin in healthy adults.
BACKGROUND
Prescription omega-3-acid ethyl esters (P-OM3) have been used as adjunctive therapy to statin drugs in patients with mixed hyperlipidemia.


OBJECTIVE
To assess the effect of concomitant administration of 4 g P-OM3 on the steady-state pharmacokinetics of the maximum recommended daily dose of atorvastatin (80 mg) in healthy volunteers.


METHODS
This was a randomized, open-label, repeated-dose, two-way crossover, drug interaction study of two treatments: 4 g of P-OM3 with 80 mg atorvastatin daily or 80 mg atorvastatin daily, each administered for 14 days under fasting conditions to 50 healthy adults.


METHODS
The primary determinants of drug interaction were the ln-transformed area under the plasma concentration versus time curve (AUCtau) and maximum measured steady-state plasma concentration (C(max,ss)) over the final 24 h dosing interval (day 14) for atorvastatin and 2-hydroxyatorvastatin. Safety assessment included clinical laboratory evaluations and adverse event reporting.


RESULTS
The extent and rate of exposure (AUCtau, C(max,ss)) to atorvastatin and its active metabolites following daily administration of P-OM3 with atorvastatin (80 mg) were similar to those following the administration of atorvastatin (80 mg) alone. Both treatments were well tolerated.


CONCLUSIONS
After 14 days of dosing, the rate and extent of exposure (AUCtau, C(max,ss)) to atorvastatin and its active metabolites were similar with both treatments, indicating that administration of P-OM3 did not affect the steady-state bioavailability of orally administered atorvastatin.
Di Spirito
M
M
MDS Pharma Services, 2350 Cohen Street, Saint-Laurent, Montreal, Quebec, H4R 2N6, Canada. mike.dispirito@mdsinc.com
Morelli
G
G
Doyle
R T
RT
Johnson
J
J
McKenney
J
J
D000328:Adult; D000069059:Atorvastatin; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D006262:Health; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics*
D015525:Fatty Acids, Omega-3; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin