Table 5.
The in vivo observed and in vitro predicted AUCm/AUCp values for seven M/P pairs.
| Parent | Metabolite | Predicted AUCm/AUCp |
Observed AUCm/ AUCp (Range) |
Predicted/ Observed (Range) |
References |
|---|---|---|---|---|---|
| Codeine | Morphine | 0.051a | 0.068a,b | 0.75 | 1, 2, 3 |
| 0.042 | 0.071 (0.019 – 0.17) | 0.60 (0.26 – 2.2) | |||
| Caffeine | Theophylline | 0.50 | 0.12 (0.11 – 0.14) | 4.0 (3.6 – 4.6) | 4, 5 |
| Imipramine | Desipramine | 1.43 | 0.89 (0.50 – 1.6) | 1.6 (0.89 – 2.9) |
6, 7, 8, 9, 10, 11, 12 |
| Clomipramine | N-desmethylclomipramine | 7.49 | 1.7 (1.2 – 2.2) | 4.3 (3.4 – 6.1) | 13, 14 |
| 8-hydroxyclomipramine | 0.22 | 0.40 (0.36 – 0.44) | 0.55 (0.49 – 0.61) | ||
| 2-hydroxyclomipramine | 0.05 | NDc | ND | ||
| Amitriptyline | Nortriptyline | 0.45 | 0.47 ( 0.43 – 0.53) | 0.91 (0.81 – 1.0) | 15, 16, 17 |
Notes: All values are for after PO administration unless otherwise noted. All observed AUCm/AUCp ratios were determined after single dose administration, save for the two in vivo studies of clomipramine. ND indicates a value not determined.
Superscript ‘a’ indicates a predicted or observed AUCm/AUCp after IV administration.
Superscript ‘b’ indicates that only one in vivo study was available.
Superscript ‘c’ indicates a value not determined because the metabolite was not detected in vivo. Reference numbers coincide with the below provided references and not with the bibliography references.
References: 1Guay et al, 1988; 2Yue et al, 1991a; 3Yue et al, 1991b; 4Akinyinka et al, 2000; 5Rodopoulos et al, 1996; 6Abernethy et al, 1984; 7Albers et al, 1995; 8Albers et al, 2000; 9Bergstrom et al, 1992; 10Koyama et al, 1994; 11Kurtz et al, 1997; 12Wells et al, 1986; 13Linnoila et al, 1982; 14Shimoda et al, 1995; 15Jiang et al, 2002; 16Liedholm et al, 1998 and 17Venkatakrishnan et al, 2001.