Single and multiple dose pharmacokinetics of nefazodone in subjects classified as extensive and poor metabolizers of dextromethorphan

British Journal of Clinical Pharmacology

Volumn 42, Issue 5, 1996, Pages 573-581

  Barbhaiya, R H ^a,b   Buch, A B ^a   Greene, D S ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b PROCTER AND GAMBLE COMPANY   (United States)

Author keywords

cytochrome P450 2D6; nefazodone; pharmacokinetics; phenotype

Indexed keywords

(3 CHLOROPHENYL)PIPERAZINE; CYTOCHROME P450; DEXTROMETHORPHAN; DRUG METABOLITE; NEFAZODONE;

ADULT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG URINE LEVEL; HUMAN; HUMAN EXPERIMENT; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; PHARMACOKINETICS; PHENOTYPE; PRIORITY JOURNAL;

EID: 0029808757     PISSN: 03065251     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1365-2125.1996.tb00051.x     Document Type: Article

References (22)

1. Feigher JP, Pambakian R, Fowler RC, Boyer WF, D'Amico MF. A comparison of nefazodone, imipramine and placebo in patients with moderate to severe depression. Psychopharmacol Bull 1989; 25: 219-221.
2. Eison AS, Eison MS, Torrente JR, Wright RN, Yocca FD. Nefazodone: Preclinical Pharmacology of a New Antidepressant. Psychopharmacol Bull 1990; 26: 311-315.
3. Kaul S, Shukla UA, Barbhaiya RH. Nonlinear pharmacokinetics of nefazodone after escalating single and multiple oral doses. J Clin Pharmacol 1995; 35: 830-839.
4. Mayol RF, Cole CA, Luke GM, Colson KL, Kerns EH. Characterization of the metabolites of the antidepressant drug nefazodone in human urine and plasma. Drug Metab Disp 1994; 22: 304-311.
5. Barbhaiya RH, Shukla UA, Greene DS. Single-dose pharmacokinetics of nefazodone in healthy young and elderly subjects with renal or hepatic impairment. Eur J Clin Pharmacol 1995; 49: 221-228.
6. Barbhaiya RH, Brady ME, Shukla UA, Greene DS. Steady-state pharmacokinetics of nefazodone in subjects with normal and impaired renal function. Eur J Clin Pharmacol 1995; 49: 229-235.
7. Barbhaiya RH, Marathe PH, Greene DS, et al. Safety, tolerance and preliminary pharmacokinetics of nefazodone after administration of single and multiple oral doses to healthy adult male volunteers: A double blind Phase I study. J Clin Pharmacol 1995; 35: 974-984.
8. Hyslop DK, Allen LE, Taylor DP. Triazolo antidepressants do not inhibit monoamine oxidase. Drug Rev Res 1988; 12: 77-79.
9. Taylor DP, Smith DW, Hyslop DK, Riblet LA, Temple DL Receptor binding and atypical antidepressant drug discovery. In Receptor Binding in Drug Research, Ed. O'Brien RA. New York: Marcel Dekker, 1986, pp. 151-165.
10. Eichelbaum M. Defective oxidation of drugs. Clin Pharmacokin 1982; 7: 1-22.
11. Guttendorf RJ, Wedland PJ. Genetic aspects of drug disposition and therapeutics, J Clin Pharmacol 1992; 32: 107-117.
12. Kalow W. Ethnic differences in drug metabolism. Clin Pharmacokin 1982; 7: 373-400.
13. Balant LP, Balant-Gorgia AE, Gex-Faly M, Eichelbaum M. Genetic polymorphisms in human drug metabolism. In New Trends in Pharmacokinetics Eds. Resigno A, Thakur AP. Plenum Press, NY, 1991, pp. 391-410.
14. Vincent-Viry M, Muller J, Fournier B, Galteau MM, Siest G. Relation between debrisoquine oxidation phenotype and morphological, biological and pathological variables in a large population, Clin Chein 1991; 37: 327-332.
15. Schmid B, Bircher J, Preisig R, Kupfer A. Polymorphic dextromethorphan metabolism: Cosegregation of oxidative O-demethylation with debrisoquin hydroxylation. Clin Pharmacol Ther 1985; 38: 618-624.
16. Henthorn TK, Benitez J, Avram MJ, Martinez C. Assessment of the debrisoquin and dextromethorphan phenotyping tests by Gaussian mixture distributions analysis. Clin Pharmacol Ther 1989; 45: 328-333.
17. Buch A, Shukla U, Pittman K, Barbhaiya R. Pharmacokinetics of nefazodone in extensive and poor metabolizers of dextromethorphan. Pharm Res 1993; 10: S314.
18. East T, Dye D. Determination of dextromethorphan and metabolites in human plasma and urine by high performance liquid chromatography with fluorescence detection. J. Chromatogr 1985; 334: 99-112.
19. Franc JE, Duncan GF, Farmen RH, Pittman KA. High performance liquid Chromatographie method for the deter-mination of nefazodone and its metabolites in human plasma using laboratory robotics. J Chromatogr 1991; 570: 129-138.
20. Gibaldi M, Perrier D. Pharmacokwetics, 2nd Ed. Marcel Dekker, pp 409-417, 1982.
21. Riegelman S, Collier P. The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time, J Pharmacokin Biopharm 1980; 8: 509-534.
22. Angeld M, Dring LG, Lancaster R, Latham A, Smith RL. Correlation between response to debrisoquine and amount of drug excreted unchanged in urine. Br J Pharmacol 1975; 55: 264P.