Table 2.
Comparison of predicted total drug clearance (CLPT) with observed clearance from clinical studies (CLobs) when stratified according to age (young = 20–40 years and elderly = 65–85 years) and gender. The mean fold error between observed and predicted total drug clearance is given in brackets next to the predicted value
| CYP-selective probe drug | Young female (ml min−1 kg−1) | Elderly female (ml min−1 kg−1) | Estimated reduction in clearance (female) | Young male (ml min−1 kg−1) | Elderly male (ml min−1 kg−1) | Estimated reduction in clearance (male) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Predicted (CLPT) | Clinical (CLobs) | Predicted (CLPT) | Clinical (CLobs) | Predicted | Clinical | Predicted (CLPT) | Clinical (CLobs) | Predicted (CLPT) | Clinical (CLobs) | Predicted | Clinical | |
| Caffeine | 1.48 (0.87) | 1.75 [24] 1.66*[25] | 1.07 (NA) | NA | 28.7% | NA | 1.35 (0.83) | 1.42 [19] 1.88* [25] | 1.01 (0.63) | 1.60 [19] | 25.2% | –12.7 to 14.9% |
| S-warfarin | 0.112 (1.47) | 0.076† [22] | 0.076 (1.90) | 0.040† [22] | 32.2% | 48.3% | 0.090 (1.88) | 0.048† [22] | 0.070 (1.15) | 0.061† [22] | 22.2% | –27.1% |
| S-mephenytoin | 4.14 (0.09) | 59.0‡ (CL/F) [23] | 2.66 (NA) | NA | 35.8% | NA | 3.53 (0.06) | 59.0‡ (CL/F) [23] | 1.54 (NA) | NA | 56.4% | NA |
| Desipramine | 10.9 (0.49) | 22.0 (CL/F) [20] | 7.32 (0.35) | 20.9 (CL/F) [20] | 33.3% | 6.0% | 9.72 (0.34) | 28.7 (CL/F) [20] | 7.27 (0.42) | 17.3 (CL/F) [20] | 25.2% | 39.7% |
| Midazolam | 5.86 (0.63) | 9.39 [21] | 4.33 (0.58) | 7.50 [21] | 26.2% | 20.2% | 4.84 (0.62) | 7.75 [21] | 3.97 (0.90) | 4.41 [21] | 18.0% | 43.1% |
*
Data are mean values excluding subjects 4, 9 and 12 (>40 years).
†
Reported CL/F taken as CL since F is assumed to be complete [36].
‡
Data are mean values for 12 volunteers (23–49 years) after weight normalization using 70 kg. NA, data not available.