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. 2012 Jun 22;74(5):873–885. doi: 10.1111/j.1365-2125.2012.04363.x

Table 5.

Comparison between observed and simulated pharmacokinetic parameters

Pregnant women Nonpregnant women Fold change from control
Observed Predicted Observed Predicted Observed Predicted
Drug PK parameter Mean (SD) Mean (total) Mean (unbound) Ratio (predicted/observed) Mean (SD) Mean (total) Mean (unbound) Ratio (predicted/observed) Mean (total) Mean (unbound) Ratio
Caffeine 150 mg oral n 8 4
Cmax (mg l–1) 4.58 (1.2) 3.26 2.67 0.71 6.02 (1.8) 3.59 2.44 0.60 ↓0.76 ↓0.91 ↑1.09 1.19
Tmax (h) 1.5 1.5 1.5 1.00 0.75† 0.97 1 1.29 ↑2.00 ↑1.55 ↑1.5 0.77
AUC24h (mg l–1 h–1) 52 47 36.41 0.91 26 24 16.36 0.92 ↑2.00 ↑1.96 ↑2.23 0.98
CL (l h–1) 2.86 (0.54) 3.19‡ – 1.12 7.17 (2.43) 6.25‡ – 0.87 ↓0.40 ↓0.51 – 1.28
Metoprolol 100 mg oral n 5
Cmax (μg l–1) 60 (61) 126 120 2.10 180 (67) 201 186 1.12 ↓0.33 ↓1.60 ↓1.55 4.8
Tmax (h) 1.7 (0.3) 0.5 0.4 0.32 1.1 (0.8)† 0.5 0.3 0.46 ↑0.65 1.00 ↓0.94 1.55
AUC12h (μg l–1 h–1) 219 (277) 414 391 1.89 835 (389) 585 516 0.70 ↓3.81 ↓1.41 ↓1.32 0.37
AUC12h (μg l–1 h–1)* 188 (67) 143 135 0.76 310 (89) 164 144 0.22 ↓1.65 ↓1.15 ↓1.07 0.70
CL (l h–1) 573.6 (162) 241.5‡ – 0.42 102.6 (23.4) 170.9‡ – 1.67 ↑5.59 ↑1.41 – 0.25
Midazolam 2 mg oral n 13 13
Cmax (μg l–1) 6.4 (2.6) 3.85 0.1 0.60 9.3 (2.0) 6.48 0.3 0.70 ↓1.45 ↓1.68 ↓2.05 1.16
Tmax (h) 0.56 (0.15) 0.36 0.36 0.65 0.54 (0.14)† 0.39 0.38 0.72 ↑0.96 ↓1.08 ↓1.05 1.12
AUC6h (μg l–1 h–1) 9.5 (4.3) 7.05 0.23 0.74 17.9 (6) 10.8 0.42 0.60 ↓1.88 ↓1.53 ↓1.86 0.81
CL (l h–1) 252 (108) 284‡ – 1.13 120 (36) 185‡ – 1.54 ↑2.10 ↑1.54 – 0.73

AUC, area under the concentration-time profile; CL, clearance; Cmax, the maximum concentration; n, number of women; Tmax, the time at which Cmax occurs.

*

For 10 mg intravenous formulation.

†

Extracted from reported figures of caffeine [24], metoprolol [28] and midazolam [29].

‡

Calculated from dose/AUC24h for caffeine, dose/AUC12h for metoprolol and dose/AUC6h for midazolam.