Food does not affect the pharmacokinetics of tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist.
Tesaglitazar is a dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist in development to treat lipid and glucose abnormalities associated with type 2 diabetes. This study evaluated the effects of food on tesaglitazar pharmacokinetics. In an open, randomized, 2-way crossover study, 20 healthy men received tesaglitazar 1 mg during fasting and after a high-fat, high-calorie breakfast. Blood samples were taken to assess pharmacokinetic variables. Systemic exposure to tesaglitazar was unaffected by food intake. Estimated ratios were 0.99 (90% confidence interval [CI], 0.94-1.04) for fed/fasted area under plasma concentration-time curve and 0.82 (90% CI, 0.78-0.86) for fed/fasted maximum plasma concentration (C(max)). Mean C(max) was approximately 18% lower (0.41 [95% CI, 0.38-0.43] versus 0.50 [95% CI, 0.47-0.53] mumol/L), and median time to C(max) was increased (2.00 vs 0.75 h) in fed versus fasted state. The median difference of t(max) was 1.25 h (P = .0001, signed-rank test). Tesaglitazar was well tolerated. Tesaglitazar pharmacokinetics is unaffected by food intake, allowing once-daily administration of tesaglitazar with or without food in clinical practice.
Samuelsson
S
S
AstraZeneca R&D Mölndal, Mölndal, Sweden.
Johansson
S
S
Halldórsdóttir
S
S
Stenhoff
H
H
Ohman
K P
KP
D000328:Adult; D000476:Alkanesulfonates / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005502:Food; D006262:Health; D006801:Humans; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010666:Phenylpropionates / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D000476:Alkanesulfonates; D047493:PPAR alpha; D047495:PPAR gamma; D010666:Phenylpropionates; C501413:tesaglitazar