^* Parameter data from [16]. V fetoplacental unit: volume of fetoplacental unit. BF fetoplacental unit: blood flow of fetoplacental unit. Ratio: volume of fetoplacental unit/blood flow of fetoplacental unit. ^** Parameter data from [7]. Average consists of Ratio (V/BF), total body water, blood volume, cardiac output, and GFR. The final average for the prediction of C_max and AUC for a gestational age (GA) was with the fraction unbound protein.

The following linear equations were developed to predict the following physiological parameters as a function of gestational age [7]. This was done because the reported physiological parameters [7] did not match with the gestational age used in this study (GA 12, 24, 30, and 36 weeks).

$\mathrm{T}\mathrm{o}\mathrm{t}\mathrm{a}\mathrm{l}\mathrm{ }\mathrm{b}\mathrm{o}\mathrm{d}\mathrm{y}\mathrm{ }\mathrm{w}\mathrm{a}\mathrm{t}\mathrm{e}\mathrm{r}=0.35\times \mathrm{G}\mathrm{A}+31.4\mathrm{ }(r^2=0.992)$

$\mathrm{C}\mathrm{a}\mathrm{r}\mathrm{d}\mathrm{i}\mathrm{a}\mathrm{c}\mathrm{ }\mathrm{o}\mathrm{u}\mathrm{t}\mathrm{p}\mathrm{u}\mathrm{t}=3.8\times \mathrm{G}\mathrm{A}+308\mathrm{ }(r^2=0.982)$

$\mathrm{G}\mathrm{F}\mathrm{R}=1.8\times \mathrm{G}\mathrm{A}+118\mathrm{ }(r^2=0.901)$

Example

An example of calculation of AUC in pregnant women for digoxin is presented. In order to predict C_max or AUC for a drug, the fraction unbound protein in plasma will be used as a product characteristic. The fraction unbound protein for digoxin is 0.75. The average for digoxin at GA at week 36 will be 1.48 (average of five ratios in Table 1 plus 0.75 = 1.48). The AUC of digoxin in non-pregnant women was 9.7 ng·hr/mL and in pregnant women in the third trimester or GA 36 weeks, the predicted AUC of digoxin was 9.3/1.48 = 6.3 ng·hr/mL. The observed AUC in pregnant women was 7.3 ng·hr/mL