High correlation was found between tramadol-O-demethylation and sparteine oxidation in 71 extensive metabolizers of sparteine (rs = 0.544). The mean metabolic ratio of tramadol O-demethylation was significantly higher in poor metabolizers of sparteine than in extensive metabolizers (4.4 vs 0.8). These in vivo results confirm that tramadol O-demethylation is carried out to a large extent by the polymorphic CYP2D6.

Following i.v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 1/min) approached liver blood flow (1.51/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.

1 In order to determine on which chromosome the gene controlling human cytochrome P-450 (debrisoquine/sparteine type) is located a linkage study of polymorphic sparteine oxidation (PSO) to various polymorphic markers was carried out. 2 Positive information for linkage between PSO and the P1 blood group was obtained with a maximal LOD-score of LOD = 3.35 for both male and female recombination fraction estimates of Om = of = 0.0. 3 The P1 blood group has been recently mapped to the long arm of chromosome 22. Thus it can be concluded that the gene controlling human cytochrome P-450 (debrisoquine/ sparteine) is situated on the long arm of chromosome 22 in close vicinity to P1.

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