RT Journal Article SR Electronic T1 PHARMACOKINETICS AND METABOLISM OF TESAGLITAZAR, A NOVEL DUAL-ACTING PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR α/γ AGONIST, AFTER A SINGLE ORAL AND INTRAVENOUS DOSE IN HUMANS JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 923 OP 929 VO 32 IS 9 A1 H. Ericsson A1 B. Hamrén A1 S. Bergstrand A1 M. Elebring A1 L. Fryklund A1 M. Heijer A1 K. P. Öhman YR 2004 UL http://dmd.aspetjournals.org/content/32/9/923.abstract AB The pharmacokinetics of tesaglitazar (GALIDA), a novel dual-acting peroxisome proliferator-activated receptor α and γ agonist, were studied in eight healthy male subjects. The subjects initially received either a single oral or intravenous (i.v.) dose of 1 mg of [14C]tesaglitazar. After a washout period, they received 1 mg of nonlabeled tesaglitazar via the alternative administration route. Serial blood samples and complete urine and feces were collected until 336 h postdose. Tesaglitazar absorption was rapid, with maximum plasma concentration (Cmax) at ∼1 h postdose, and the absolute bioavailability was approximately 100%, suggesting no, or negligible, first-pass metabolism. Mean plasma clearance was 0.16 l/h and the volume of distribution at steady state was 9.1 liters. After either route of administration, the plasma concentration-time profiles of radioactivity and tesaglitazar were virtually identical, indicating low systemic metabolite concentrations and formation rate limitation of metabolite elimination. The elimination half-life of radioactivity and tesaglitazar was ∼45 h. Radioactivity recovery was complete in all subjects, with mean values of 99.9% (i.v.) and 99.6% (oral). Tesaglitazar was mainly metabolized before excretion, and most radioactivity (91%) was recovered in urine. Approximately 20% of the dose was recovered unchanged after either administration route, resulting in a renal clearance of 0.030 l/h. Most of the radioactivity in urine was identified as acyl glucuronide of tesaglitazar. Plasma protein binding of tesaglitazar was high (∼99.9%), and the mean blood-plasma partitioning ratio was 0.66, suggesting low affinity for red blood cells. There was no indication of partial inversion of the (S)-enantiomer to the corresponding (R)-form. Tesaglitazar was well tolerated. The American Society for Pharmacology and Experimental Therapeutics