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

Drug Metabolism and Disposition

Volumn 32, Issue 9, 2004, Pages 923-929

  Ericsson, Hans ^a   Hamren B ^a   Bergstrand, S ^a   Elebring, M ^a   Fryklund, L ^a   Heijer, M ^a   Ohman K P ^a  

^a ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL GLUCURONIDE; CARBON 14; GLUCURONIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; TESAGLITAZAR; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BINDING AFFINITY; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COUGHING; CROSSOVER PROCEDURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG URINE LEVEL; ENANTIOMER; ERYTHROCYTE; HUMAN; HUMAN EXPERIMENT; ISOTOPE LABELING; KIDNEY CLEARANCE; MALE; NORMAL HUMAN; OPEN STUDY; PRIORITY JOURNAL; RADIOACTIVITY; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; THORAX PAIN;

ADMINISTRATION, ORAL; ADULT; ALKANESULFONATES; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; CARBON RADIOISOTOPES; CROSS-OVER STUDIES; DRUG ADMINISTRATION SCHEDULE; FECES; HUMANS; INJECTIONS, INTRAVENOUS; MALE; MIDDLE AGED; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; PHENYLPROPIONATES; TIME FACTORS;

EID: 4143105000     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (18)

1. Andersson TB, Sjoberg H, Hoffmann KJ, Boobis AR, Watts P, Edwards RJ, Lake BG, Price RJ, Renwick AB, Gomez-Lechon MJ, et al. (2001) An assessment of human liver-derived in vitro systems to predict the in vivo metabolism and clearance of almokalant. Drug Metab Dispos 29:712-720.
2. Cronet P, Petersen JF, Folmer R, Blomberg N, Sjoblom K, Karlsson U, Lindstedt EL, and Bamberg K (2001) Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family. Structure 9:699-706.
3. Ericsson H, Bergstrand S, Fryklund L, Hamren B, Heijer M, and Ohman PK (2003) Pharmacokinetics of tesaglitazar (GALIDA™) in healthy male subjects (Abstract). Diabetes 52 (Suppl 1):P-508.
4. Ethell BT, Beaumont K, Rance DJ, and Burchell B (2001) Use of cloned and expressed human UDP-glucuronosyltransferases for the assessment of human drug conjugation and identification of potential drug interactions. Drug Metab Dispos 29:48-53.
5. Fagerberg B, Edwards S, Halmos T, Lopantynski J, Schuster H, Stender S, Stoa-Birketvedt G, Tonstad S, and Gause-Nilsson I (2003) Tesaglitazar (GALIDA) improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population (Abstract). Diabetologia 46 (Suppl 2):175.
6. Gilissen RA, Bamaby RJ, and Kajbaf M (2000) Identification of UDP-glucuronosyltransferases involved in the human hepatic metabolism of GV150526, a novel glycine antagonist. Drug Metab Drug Interact 16:173-189.
7. Izumi T, Hosiyama K, Enomoto S, Sasahara K, and Sugiyama Y (1997) Pharmacokineties of troglitazone, an antidiabetic agent: prediction of in vivo stereoselective sulfation and glucuronidation from in vitro data. J Pharmacol Exp Ther 280:1392-1400.
8. Lautala P, Ethell BT, Taskinen J, and Burchell B (2000) The specificity of glucuronidation of entacapone and tolcapone by recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos 28:1385-1389.
9. Lin JH and Wong BK (2002) Complexities of glucuronidation affecting in vitro in vivo extrapolation. Curr Drug Metab 3:623-646.
10. Ljung B, Bamberg K, Dahllof B, Kjellstedt A, Oakes ND, Ostling J, Svensson L, and Camejo G (2002) AZ 242, a novel PPARalpha/gamma agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats. J Lipid Res 43:1855-1863.
11. Prueksaritanont T, Zhao JJ, Ma B, Roadcap BA, Tang C, Qiu Y, Liu L, Lin JH, Pearson PG, and Baillie TA (2002) Mechanistic studies on metabolic interactions between gemfibrozil and statins. J Pharmacol Exp Ther 301:1042-1051.
12. Roberts MS, Magnusson BM, Burczynski FJ, and Weiss M (2002) Enterohepatic circulation: physiological, pharmacokinetic and clinical implications. Clin Pharmacokinetic 41:751-790.
13. Rubin K, Andersson TB, and Masimirembwa C (2003) Tesaglitazar (GALIDA™) does not inhibit the major drug-metabolizing cytochrome P450 enzyme systems (Abstract). Diabetes 52 (Suppl 1):P-540.
14. Samuelsson S, Bergh S, Ohman PK, and Ericsson H (2003) Food does not affect the pharmacokinetics of tesaglitazar (GALIDA™) (Abstract). Diabetes 52 (Suppl 1):P-567.
15. Soars MG, Burchell B, and Riley RJ (2002) In vitro analysis of human drug glucuronidation and prediction of in vivo metabolic clearance. J Pharmacol Exp Ther 301:382-390.
16. Spahn-Langguth H and Benet LZ (1992) Acyl glucuronides revisited: is the glucuronidation process a toxification as well as a detoxification mechanism? Drug Metab Rev 24:5-47.
17. Svennberg H, Bergh S, and Stenhoff H (2003) Factorial design for the development of automated solid-phase extraction in the 96-well format for determination of tesaglitazar, in plasma, by liquid chromatography-mass spectrometry. J Chromatogr B 787:231-241.
18. Wagner J (1976) Linear pharmacokinetic equation allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of polyexponential equations which have been fitted to the data. J Pharmacokinet Biopharm 4:443-467.