Characterisation of the human liver in vitro metabolic pattern of artemisinin and auto-induction in the rat by use of nonlinear mixed effects modelling

Biopharmaceutics and Drug Disposition

Volumn 24, Issue 2, 2003, Pages 71-85

  Svensson, Ulrika S H ^a   Mäki Jouppila, Mika ^a   Hoffmann, Kurt Jürgen ^b   Ashton, Michael ^a,c  

^a UPPSALA UNIVERSITY   (Sweden)

^b ASTRAZENECA R AND D   (Sweden)

^c UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

Artemisinin; Auto induction; CYP450; Metabolism; Nonlinear mixed effects modelling

Indexed keywords

ARTEMISININ; CARBON 14; CYTOCHROME P450 2A6; CYTOCHROME P450 2B6; CYTOCHROME P450 3A4; DRUG METABOLITE; DRUG VEHICLE; MW 282; PLACEBO;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; B LYMPHOBLAST; CELL LINE; CELL TRANSFORMATION; CONTROLLED STUDY; DATA ANALYSIS; DRUG METABOLISM; ENZYME ACTIVITY; HUMAN; HUMAN CELL; IN VITRO STUDY; INCUBATION TIME; LIVER MICROSOME; MALE; NONHUMAN; NONLINEAR SYSTEM; RADIOMETRY; RAT; STATISTICAL MODEL;

ANIMALS; ANTIMALARIALS; ARTEMISININS; ARYL HYDROCARBON HYDROXYLASES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; MALE; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; MODELS, BIOLOGICAL; NONLINEAR DYNAMICS; OXIDOREDUCTASES, N-DEMETHYLATING; RATS; RATS, SPRAGUE-DAWLEY; SESQUITERPENES; TIME FACTORS;

EID: 0037340331     PISSN: 01422782     EISSN: None     Source Type: Journal    
DOI: 10.1002/bdd.342     Document Type: Article

References (17)

1. Ashton M, Sy N, Gordi T, Hai T, Thach D, Huong N. Evidence for time-dependent artemisinin kinetics in adults with uncomplicated malaria. Pharm Pharmacol Lett 1996; 6: 127-130.
2. Hassan Alin M, Ashton M, Kihamia CM, Mtey GJ, Bjorkman A. Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients. Trans R Soc Trop Med Hyg 1996; 90(1): 61-65.
3. Ashton M, Hai TN, Sy ND, Huong DX, Van Huong N, Nieu NT, et al. Artemisinin pharmacokinetics is time-dependent during repeated oral administration in healthy male adults. Drug Metab Dispos 1998; 26(1): 25-27.
4. Svensson USH, Ashton M. Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol 1999; 48(4): 528-535.
5. Ramu K, Baker JK. Synthesis, characterization, and antimalarial activity of the glucuronides of the hydroxylated metabolites of arteether. J Med Chem 1995; 38(11): 1911-1921.
6. Svensson USH, Sandstrom R, Carlborg O, Lennernas H, Ashton M. High in situ rat intestinal permeability of artemisinin unaffected by multiple dosing and with no evidence of P-glycoprotein involvement. Drug Metab Dispos 1999; 27(2): 227-232.
7. Lowry O, Rosebrough A, Farr A, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275.
8. Edlund PO, Westerlund D, Carlqvist J, Wu BL, Jin YH. Determination of artesunate and dihydroartemisinine in plasma by liquid chromatography with post-column derivatization and UV-detection. Acta Pharm Suec 1984; 21(4): 223-234.
9. Beal S, Sheiner L. NONMEM Users' Guides, NONMEM Project Group, University of California at San Francisco, San Francisco. 1998.
10. Karlsson MO, Sheiner LB. The importance of modeling interoccasion variability in population pharmacokinetic analyses. J Pharmacokinet Biopharm 1993; 21(6): 735-750.
11. Jonsson EN, Karlsson MO. Xpose-an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM. Comput Methods Programs Biomed 1999; 58(1): 51-64.
12. Wahlby U, Jonsson EN, Karlsson MO. Assessment of actual significance levels for covariate effects in NONMEM. J Pharmacokinet Pharmacodyn 2001; 28(3): 231-252.
13. Manly B. In Randomization, Bootstrap and Monte Carlo Methods in Biology. (2nd edn). Chapman & Hall: London, 1997.
14. Svensson USH, Ashton M, Trinh NH, Bertilsson L, Dinh XH, Nguyen VH, et al. Artemisinin induces omeprazole metabolism in human beings. Clin Pharmacol Ther 1998; 64(2): 160-167.
15. Chang TK, Yu L, Maurel P, Waxman DJ. Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: Response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. Cancer Res 1997; 57(10): 1946-1954.
16. Ashton M, Johansson L, Thornqvist AS, Svensson US. Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat. Xenobiotica 1999; 29(2): 195-204.
17. Gupta S, Svensson USH, Ashton M. In vitro evidence for auto-induction of artemisinin metabolism in the rat. Eur J Drug Metab Pharmacokinet 2001; 26: 173-178.