Abstract
Polymorphic differences in dextromethorphan metabolism were observed in three studies conducted in a total of 44 subjects (of Dutch origin) administered 60 mg dextromethorphan hydrobromide as an OROS tablet. Mean plasma dextromethorphan (DM) concentrations after a single dose and at steady state were 4–75 times higher in the poor metabolizers (PM) relative to the extensive metabolizers (EM). Following a single dose, the mean areas under the plasma concentration–time curve (AUC, 0–24 hr) of DM, total dextrorphan (DR), and total 3-hydroxymorphinan (HM) were 6.9-fold higher, 17.4-fold lower, and 11-fold lower, respectively, for the PM than for the EM. Correspondingly, steady-state AUC values were 52.8 times higher, 6.7 times lower, and 3.3 times lower for DM, total DR, and total HM, respectively, for the PM relative to the EM. Drug/metabolite ratios (DMR) for amounts excreted in the urine of DR and HM indicated polymorphism in O-demethylation of DM since DMR for PM was 352 and 338 times higher than that for EM for DR and HM, respectively. However, polymorphism in N-demethylation was not observed. Ratios of conjugated/free dextrorphan and 3-hydroxymorphinan excreted in the urine suggest also a lack of conjugative capacity in the PM, relative to the EM. The overall incidence of PM was 9.1% in this population.
Similar content being viewed by others
REFERENCES
A. Mahgoub, J. R. Idle, L. G. Dring, R. Lancaster, and R. L. Smith. Lancet 2:584–586 (1977).
M. Eichelbaum, L. Bertilsson, J. Sawe, and C. Zekorn. Clin. Pharmacol. Ther. 31(2):184–186 (1982).
D. A. P. Evans, D. Harmer, D. Y. Downham, E. J. Whibley, J. R. Idle, J. Ritchie, and R. L. Smith. J. Med. Gen. 20:321–329 (1983).
S. D. Roy, E. M. Hawes, J. W. Hubbard, G. McKay, and K. K. Midha. Lancet 2:1393 (1984).
R. L. Woosley, D. M. Roden, G. Dai, T. Wang, D. Atenbern, J. Oates, and G. R. Wilkinson. Clin. Pharmacol. Ther. 39(3):282–287 (1986).
D. E. Drayer and M. M. Reidenberg. Clin. Pharmacol. Ther. 22(3):251–258 (1977).
P. J. Wedlund, W. S. Aslanian, C. B. McAllister, G. R. Wilkinson, and R. A. Branch. Clin. Pharmacol. Ther. 36(6):773–780 (1984).
A. Kupfer and R. Preisig. Eur. J. Clin. Pharmacol. 26:753–759 (1984).
A. Kupfer, B. Schmid, and G. Pfaff. Xenobiotica 16(5):421–433 (1986).
B. Schmid, J. Bircher, R. Preisig, and A. Kupfer. Clin. Pharmacol. Ther. 38(6):618–624 (1985).
J. H. G. Jonkman (in press).
E. Jacqz, S. D. Hall, R. A. Branch, and G. R. Wilkinson. Clin. Pharmacol. Ther. 39(6):646–653 (1986).
W. M. Benson, P. L. Stefko, and L. O. Randall. J. Pharmacol. Ther. 109:189–200 (1953).
A. Kupfer, B. Schmid, R. Preisig, and G. Pfaff. Lancet 2:517–518 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vetticaden, S.J., Cabana, B.E., Prasad, V.K. et al. Phenotypic Differences in Dextromethorphan Metabolism. Pharm Res 6, 13–19 (1989). https://doi.org/10.1023/A:1015835215945
Issue Date:
DOI: https://doi.org/10.1023/A:1015835215945