Microsomal binding of amitriptyline: Effect on estimation of enzyme kinetic parameters in vitro

Journal of Pharmacology and Experimental Therapeutics

Volumn 293, Issue 2, 2000, Pages 343-350

  Venkatakrishnan, Karthik ^a,b   Von Moltke, Lisa L ^a,b   Obach, R Scott ^c   Greenblatt, David J ^a,b  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b TUFTS MEDICAL CENTER   (United States)

^c PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMITRIPTYLINE; CYTOCHROME P450 ISOENZYME;

ARTICLE; BINDING AFFINITY; DRUG BINDING; DRUG TRANSFORMATION; ENZYME KINETICS; HUMAN; HUMAN CELL; HUMAN TISSUE; LIVER MICROSOME; MODEL; PRIORITY JOURNAL; PROTEIN ANALYSIS;

ALGORITHMS; AMITRIPTYLINE; ANTIDEPRESSIVE AGENTS, TRICYCLIC; ARYL HYDROCARBON HYDROXYLASES; BIOTRANSFORMATION; CYTOCHROME P-450 ENZYME SYSTEM; DEALKYLATION; DIALYSIS; HUMANS; KINETICS; LEUKEMIA, LYMPHOCYTIC; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; TUMOR CELLS, CULTURED;

EID: 0034109883     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (20)

1. Abernethy DR, Greenblatt DJ and Shader RI (1981) Tricyclic antidepressant determination in human plasma by gas-liquid chromatography using nitrogen-phosphorous detection: Application to single-dose pharmacokinetic studies. Pharmacology 23:57-63.
2. Carlile DJ, Hakooz N, Bayliss MK and Houston JB (1999) Microsomal prediction of in vivo clearance of CYP2C9 substrates in humans. Br J Clin Pharmacol 47:625-635.
3. Ghahramani S, Ellis SW, Lennard MS, Ramsay LE and Tucker GT (1997) Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol 43:137-144.
4. Gibbs MA, Kunze KL, Howald WN and Thummel KE (1999) Effect of inhibitor depletion on inhibitor potency: Tight binding inhibition of CYP3A by clotrimazole. Drug Metab Dispos 27:596-599.
5. m values: Implications for clinical correlation. J Pharmacol Exp Ther 282:391-396.
6. Obach RS (1996) The importance of nonspecific binding in in vitro matrices, its impact on enzyme kinetic studies of drug metabolism reactions, and implications for in vitro-in vivo correlations. Drug Metab Dispos 24:1047-1049.
7. Obach RS (1997) Nonspecific binding to microsomes: Impact on scale-up of in vitro intrinsic clearance to hepatic clearance as assessed through examination of warfarin, imipramine, and propranolol. Drug Metab Dispos 25:1359-1369.
8. Obach RS (1999) The prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data. An examination of the in vitro half-life approach and non-specific binding to microsomes. Drug Metab Dispos 27: 1350-1359.
9. Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ and Wastall P (1991) The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J Pharmacol Exp Ther 283:46-58.
10. Olesen OV and Linnet. K (1997) Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. Pharmacology 55: 235-243.
11. Schmider J, Greenblatt DJ, Harmatz JS and Shader RI (1996) Enzyme kinetic modeling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: Application to amitriptyline N-demethylation. Br J Clin Pharmacol 41:593-604.
12. Schmider J, Greenblatt DJ, von Moltke LL, Harmatz JS and Shader RI (1995) AT-Demethylation of amitriptyline in vitro: Role of cytochrome P-450 3A (CYP3A) isoforms, and effect of metabolic inhibitors. J Pharmacol Exp Ther 275:592-597.
13. Schulz P, Dick P, Blaschke TF and Hollister L (1985) Discrepancies between pharmacokinetic studies of amitriptyline. Clin Pharmacokinet 10:257-268.
14. Shimada T, Yamazaki H, Mimura M, Inui Y and Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423.
15. Venkatakrishnan K, Greenblatt DJ, von Moltke LL, Schmider J, Harmatz JS and Shader RI (1998) Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: Dominance of CYP 2C19 and 3A4. J Clin Pharmacol 38:112-121.
16. Venkatakrishnan K, von Moltke LL and Greenblatt DJ (1999) Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low-affinity): Implications for interactions with enzyme-inducing drugs. J Clin Pharmacol 39:567-577.
17. von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Duan SX, Harmatz JS and Shader RI (1994) Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: A model system to predict drug interactions in vivo. J Pharmacol Exp Ther 268:1278-1283.
18. von Moltke LL, Greenblatt DJ, Harmatz JS and Shader RI (1993) Alprazolam metabolism in vitro: Studies of human, monkey, mouse, and rat liver microsomes. Pharmacology 47:268-276.
19. Witherow LE and Houston JB (1999) Sigmoidal kinetics of CYP3A substrates: An approach for scaling dextromethorphan metabolism in hepatic microsomes and isolated hepatocytes to predict in vivo clearance in the rat. J Pharmacol Exp Ther 290:58-65.
20. Wright JD, Boudinot FD and Ujhelyi MR (1996) Measurement and analysis of unbound drug concentrations. Clin Pharmacokinet 30:445-462.