Introduction and Gestational Pharmacokinetic Methodology

Mechanism

Throughout this vademecum, the kinetic parameters are analyzed considering the following alterations of the pregnant organism:

Pharmacokinetics

Alterations of the Gravid Distribution Model

1. Plasma volume: It expands between 30% and 50% from the sixth week, increasing the volume of distribution (V_d) of hydrophilic drugs.
2. Serum albumin: It decreases by hemodilution, which increases the free active fraction of active ingredients with high binding to plasma proteins (e.g., phenytoin, magnesium sulfate).
3. Glomerular Filtration (GFR): Renal plasma flow and GFR increase up to 50%, accelerating the clearance of active ingredients eliminated unchanged through urine.
4. Hepatic metabolism: Progesterone selectively induces key cytochrome P450 isoenzymes, notably CYP3A4, CYP2D6 and CYP2C9, while decreasing the activity of CYP1A2.

Likewise, the transplacental passage is governed by the molecular weight of the drug (molecules < 500 Da cross freely by passive diffusion), its degree of ionization (the fetal pH is slightly more acidic than the maternal one, which can cause ionic trapping of weak bases) and the expression of placental efflux transporters such as P-glycoprotein (P-gp).