Table 1.
Influence of UGT2B15 D85Y genotype on oxazepam pharmacokinetic and pharmacodynamic parameters measured in 30 male subjects
| UGT2B15 D85Y genotype | ||||
|---|---|---|---|---|
| Parameter (units) | DD (n= 6) | DY (n= 20) | YY (n= 4) | anova (P-value) |
| Cmax (ng ml−1) | 177 (152–200) | 208a (169–257) | 269a (228–288) | 0.011 |
| Tmax (h) | 2.0 (1.4–2.6) | 2.0 (1.5–2.9) | 2.5 (1.3–3.0) | 0.65 |
| t1/2 (h) | 5.5 (4.7–9.7) | 5.5 (4.6–7.4)b | 9.5 (6.8–11.2)b | 0.040 |
| AUCtotal (µg ml−1 h−1) | 0.93cd (0.77–1.20) | 1.37ce (0.98–1.69) | 2.26de (1.76–3.48) | <0.001 |
| CL/F (ml min−1 kg−1) | 3.35fg (2.84–4.17) | 2.34fh (2.00–3.30) | 1.62gh (0.95–2.10) | 0.003 |
| EEG AUEC0–8h (change h−1) | 25.7 (8.3–38.2) | 17.9 (4.1–50.0) | −6.26 (−36.3–49.0) | 0.67 |
| DSST AUEC0–8h (change h−1) | 37.3 (−8.4–87) | 62.8 (30.2–105) | 56.1 (−28.4–103) | 0.53 |
| OBS AUEC0–8h (change h−1) | 18.3 (6.0–40.3) | 32.9 (7.9–62.6) | 33.5 (5.3–257) | 0.68 |
| SED AUEC0–8h (change h−1) | 24.4 (−62.4–82.6) | 14.6 (−65.6–86.1) | 5.2 (−107–51.1) | 0.83 |
AUEC, area under the effect curve; EEG, electroencephalogram relative β wave amplitude; DSST, digit-symbol substitution test; OBS, observer-rated sedation score; SED, subject-rated sedation score.
a–h
Identifies median values that are significantly different from each other (P < 0.05) by Student–Newman–Keuls pair-wise multiple comparisons testing. Tmax, t1/2 and AUCtotal values were log transformed and AUEC values were rank transformed since data were not normally distributed. Shown for each parameter are the genotype group median (interquartile range) values and the P-value of group comparisons by anova.