Dose dependency of dextromethorphan for cytochrome P450 2D6 (CYP2D6) phenotyping

Clinical Pharmacology and Therapeutics

Volumn 66, Issue 5, 1999, Pages 535-541

  Streetman, Daniel S ^a,b   Ellis, Ross E ^a,b   Nafziger, Anne N ^a,b   Leeder, J Steven ^a,b   Gaedigk, Andrea ^a,b   Gotschall, Russell ^a,b   Kearns, Gregory L ^a,b   Bertino Jr , Joseph S ^a,b,c  

^a BASSETT HEALTHCARE   (United States)

^b CHILDREN S MERCY HOSPITAL   (United States)

^c BASSETT RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DEBRISOQUINE 4 HYDROXYLASE; DEXTROMETHORPHAN; GUAIFENESIN;

ADULT; ARTICLE; DOSE RESPONSE; DRUG ELIMINATION; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG URINE LEVEL; ENZYME ACTIVITY; FEMALE; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; PHENOTYPE; PRIORITY JOURNAL;

EID: 0032752586     PISSN: 00099236     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0009-9236(99)70018-4     Document Type: Article

References (22)

1. 1. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. 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 1994;270:414-23.
2. 2. Rendic S, Di Carlo FJ. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 1997;29:413-580.
3. 3. Schmid B, Bircher J, Preisig R, Kupfer A. Polymorphic dextromethorphan metabolism: co-segregation of oxidative O-demethylation with debrisoquin hydroxylation. Clin Pharmacol Ther 1985;38:618-24.
4. 4. Kupfer A, Schmid B, Pfaff G. Pharmacogenetics of dextromethorphan O-demethylation in man. Xenobiotica 1986;16:421-33.
5. 5. Schadel M, Wu H, Otton SV, Kalow W, Sellers EM. Pharmacokinetics of dextromethorphan and metabolites in humans: influence of the CYP2D6 phenotype and quinidine inhibition. J Clin Psychopharmacol 1995;15:263-9.
6. 6. Vetticaden SJ, Cabana BE, Prasad VK, Purich ED, Jonkman JHJ, de Zeeuw R, et al. Phenotypic differences in dextromethorphan metabolism. Pharm Res 1989;6:13-9.
7. 7. Capon DA, Bochner F, Kerry N, Mikus G, Danz C, Somogyi AA. The influence of CYP2D6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans. Clin Pharmacol Ther 1996; 60:295-307.
8. 8. Mortimer O, Lindstrom B, Laurell H, Bergman U, Rane A. Dextromethorphan: polymorphic serum pattern of the O-demethylated and di-demethylated metabolites in man. Br J Clin Pharmacol 1989;29:223-7.
9. 9. Zhang Y, Britto MR, Valderhaug KL, Wedlund PJ, Smith RA. Dextromethorphan: enhancing its systemic availability by way of low-dose quinidine-mediated inhibition of cytochrome P4502D6. Clin Pharmacol Ther 1992;51: 647-55.
10. 10. von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Venkatakrishnan K, Schmider J, et al. Multiple human cytochromes contribute to biotransformation of dextromethorphan in vitro: role of CYP2C9, CYP2C19, CYP2D6, and CYP3A. J Pharm Pharmacol 1998;50:997-1004.
11. 11. Schmider J, Greenblatt DJ, Fogelman SM, von Moltke LL, Shader RI. Metabolism of dextromethorphan in vitro: involvement of cytochromes P450 2D6 and 3A3/4, with a possible role of 2E1. Biopharm Drug Dispos 1997; 18:227-40.
12. 12. Hollander D, Pradas J, Kaplan R, McLeod HL, Evans WE, Smith RA. High-dose dextromethorphan in amyotrophic lateral sclerosis: phase I safety and pharmacokinetic studies. Ann Neurol 1994;36:920-4.
13. 13. Park YH, Kullberg MP, Hinsvark ON. Quantitative determination of dextromethorphan and three metabolites in urine by reverse-phase high-performance liquid chromatography. J Pharm Sci 1984;73:24-9.
14. 14. Lam YW, Rodriguez SY. High-performance liquid chromatography determination of dextromethorphan and dextrorphan for oxidation phenotyping by fluorescence and ultraviolet detection. Ther Drug Monit 1993;15:300-4.
15. 15. Kashuba ADM, Nafziger AN, Kearns GL, Leeder JS, Shirey CS, Gotschall R, et al. Quantification of three-month intraindividual variability and the influence of menstrual cycle phase on CYP2D6 activity as measured by dextromethorphan phenotyping. Pharmacogenetics 1998;8:403-10.
16. 16. Brosen K. Recent developments in hepatic drug oxidation: implications for clinical pharmacokinetics. Clin Pharmacokinet 1990;18:220-39.
17. 17. Sloan TP, Lancaster R, Shah RR, Idle JR, Smith RL. Genetically determined oxidation capacity and the disposition of debrisoquine. Br J Clin Pharmacol 1983;15: 443-50.
18. 18. Brosen K, Gram LF. First-pass metabolism of imipramine and desipramine: impact of the sparteine oxidation phenotype. Clin Pharmacol Ther 1988;43:400-6.
19. 19. Lee JT, Kroemer HK, Silberstein DJ, Funck-Brentano C, Lineberry MD, Wood AJ, et al. The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. N Engl J Med 1990; 322:1764-8.
20. 20. Siddoway LA, Thompson KA, McAllister CB, Wang T, Wilkinson GR, Roden DM, et al. Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation 1987;75: 785-91.
21. 21. Connolly SJ, Kates RE, Lebsack CS, Harrison DC, Winkle RA. Clinical pharmacology of propafenone. Circulation 1983;68:589-96.
22. 22. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK. Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites. Mol Pharmacol 1993;43:120-6.