Chapter 17 - Page 2 - Java 1
Linear Plot of Morphine Concentration versus Time after Codeine Administration
Try simulating morphine concentration versus time after oral codeine administration. Select individuals with low, intermediate or high CYP2D6 activity.
Add additional lines with different parameter values using the Add Line button.
Figure 1701a A Simplified Pharmacokinetic Model for Codeine Transformation into Morphine
The model in Figure 1701a is a simplification of codeine and morphine pharmacokinetics. Codeine is metabolized to a variety of compounds including morphine. Also, both codeine and morphine are probably better described using a two compartment model.
The lines in the plot above were calculated using Equation 1701a, derived from the model, Figure 1701a, for codeine metabolism using Laplace transforms.
Equation 1701a Concentration of Morphine after Oral Administration of Codeine
Table 1701a Some Parameters Describing Codeine Metabolism
References and Notes
- 1Ritschel, W.A. and Kearns, G.L. 2004 Handbook of Basic Pharmacokinetics ... including Clinical Applications, 6th ed., American Pharmaceutical Association, Washington, DC ISBN 1-58212-054-4
- 2Estimated from kel and tmax (1.1 and 1.2 hr)3,4
- 3Band, C.J., Band, P.R., Deschamps, M., Besner, J.G. and Coldman, A.J. 1994 Human pharmacokinetic study of immediate-release and sustained-release codeine, J. Clin. Pharmacol., 34, 938-43
- 4Shah, J.C. and Mason, W.D. 1990 Plasma codeine and morphine concentrations after a single oral dose of codeine phosphate, J. Clin. Pharmacol., 30, 764-6
- 5Estimated from kel and fe (0.071, 0.051 and 0.065)6,7,8
- 6Chen, Z.R., Somogyi, A.A., Reynolds, G. and Bochner, F. 1991 Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers, Brit. J. Clin. Pharmacol., 31, 381-90
- 7Vree, T.B. and Verwey-van Wissen, C.P. 1992 Pharmacokinetics and metabolism of codeine in humans, Biopharm. Drug Disposit., 13, 445-60
- 8Hendenmalm, K., Sundgren, M., Granberg, K., Spigset, O. and Dahlqvist, R. 1997 Urinary excretion of codeine, ethylmorphine, and their metabolites: Relation to the CYP2D6 activity, Therap. Drug Monitor., 19, 643-9
- 9Estimated as 0.5 x km (high)
- 10Estimated from km (high) and plasma and urine ratios (1:0.034 and 0.058)11,6
- 11Desmeules, J., Gascon, M.P., Dayer, P. and Magistris, M. 1991 Impact of environmental and genetic factors on codeine analgesia, Eur. J. Clin. Pharmacol., 41, 23-6
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