Physiological changes in pregnancy

Many physiological changes during pregnancy can affect the pharmacokinetics/pharmacodynamics (PK/PD) of aminoglycosides. In this step, we provide an overview of the main changes and explain their impact on aminoglycosides.

The most obvious visual change in pregnancy is weight gain. This is mostly due to the growing foetus, but the woman herself also gains weight in the form of fat and water. This additional water is found in the blood, through an increase in blood volume and also extravascularly, in the uterus and additional fat. Overall, the volume of districution (Vd) is increased in pregnant women, and distribution to the foetus also needs to be considered.

The increased blood volume is accompanied by a decrease in serum albumin. This can lead to an increase in the amount of free, usually highly protein-bound drug present in the blood so that they are more effective and can be cleared and metabolised faster.

Blood flow through the kidneys, and therefore GFR, increases, resulting in an increase in renal function of around 50%. This change occurs within the first few weeks of pregnancy and continues until after delivery. Liver metabolism also increases, but this is less predictable and highly variable between each woman. Additional metabolism pathways are also present in the placenta and umbilical cord, to protect the unborn baby. Therefore, it should be expected that pregnant women may metabolise and clear a number of drugs quicker than those who are not pregnant.

Effect on aminoglycosides

The half-life of aminoglycosides is greatly reduced in pregnant women; for gentamicin, it is approximately halved, from 2.5-4 hours to 1.5-2 hours.

Aminoglycoside PK, such as blood concentrations and clearance, are more closely related to the increased Vd rather than the increased renal clearance. Although renal clearance is increased, the distribution of aminoglycosides into extravascular fluid means they cannot be cleared by the kidneys until they redistribute back into the blood.

The molecular weight and size of aminoglycosides are small enough for them to cross the blood placental barrier to reach the foetus. This supply of aminoglycoside via the placenta, coupled with the PK profile of the foetus (very similar to neonates, see step 3.6) means aminoglycoside blood concentrations in the foetus reach around one-third of that of the maternal blood.

However, aminoglycoside PK in pregnancy can be unpredictable, so care is needed to use these antibiotics safely, as we will see on the next page.