FIGURES AND TABLES

Figure 1.

Concentration–time curves (mean and standard deviation) of codeine and the O-demethylated codeine metabolites morphine, M3G and M6G. Red lines correspond to the mean plasma concentrations of the UM group, blue lines to the means of the EM group and green lines to the means of the PM group.

Figure 2.

Ratio of plasma AUC of morphine over plasma AUC or codeine in relation to the CYP2D6 activity expressed by the number of active alleles differentiating between fully active alleles, which were considered with one arbitrary activity unit, and alleles with reduced activity, with were arbitrarily considered, which 0.5 activity units.

Figure 3.

Correlation between the plasma morphine/codeine ratio and the oral total clearance of metoprolol, a phenotyping substance for CYP2D6 activity. Green dots depict the PMs, blue dots depict the EMs and red dots depict the UMs as defined in Table 1. The data for metoprolol were taken from Kirchheiner et al. ¹³ In fact, the participants of the present study were also UMs according to metoprolol CYP2D6 metabolic phenotype but there is no strict antimode between EM and UM, that is, there is an overlap of the ranges of phenotypes and there is apparently some scatter, probably partially owing to interindividual variation in daily CYP2D6 activity and partially owing to specific factors (other enzymes, transporters) specifically relevant for one or the other probe drug.

Table 1 - CYP2D6 and -opioid receptor genotypes of the study participants and phenotypical classifications (phenotype groups UM, EM, PM and fine activity groups).

Table 2 - Pharmacokinetic parameters in plasma of codeine and its O-demethylated metabolites.