17 Pharmacokinetics in pregnancy

Metabolism and kinetics of medicinal products are more complicated in pregnancy than otherwise. In general, the effective concentration of a drug or its metabolites is influenced by the following:

■ the uptake, distribution, metabolism and excretion by the mother (changes during pregnancy of some physiologic parameters influencing the metabolism of chemicals are summarized in Table 1.2)

■ the passage and metabolism through the yolk sac and the placenta

■ the distribution, metabolism and excretion by the embryo or fetus

■ re-absorption and swallowing of substances by the unborn from the amniotic fluid.

Pregnancy induces many maternal physiological changes and adaptations, which can lead to clinically important reductions in the blood concentrations of certain medicinal products. The total

Table 1.2. Change; during pregnancy of the pharmacokinetics of drugs

Resorption

Gastrointestinal motility 1

Lung function Î

Skin blood circulation

Distribution

Plasma volume

Body water

Plasma protein 1

Fat deposition

Metabolism

Liver activity î 1

Excretion

Glomerular filtration

Source: Loebstein (1997).

body water increases by as much as 81 during pregnancy, which provides a substantially increased volume in which drugs can be distributed. During pregnancy, the intestinal, cutancous and inhala-tory absorption of chemicals changes due to a decreased peristalsis of the intestines and an increase in skin and lung blood flow. However, this has no consequences for the uptake of medicines from the intestinal tract. Serum proteins relevant to drug binding undergo considerable changes in concentration. Albumin, which binds acidic drugs and chemicals {such as phenytoin and aspirin), decreases in concentration by up to lOg/l. The main implication of this change is in the interpretation of drug concentrations. The increased production of female hormones activates enzymes in the maternal liver, and this may result in a modified inactivation of medicinal and environmental agents. The renal plasma flow will have almost doubled by the last trimester of pregnancy, and drugs that are eliminated unchanged by the kidney are usually eliminated more rapidly; this change in renal clearance has been clinically important in only a few cases, and does not require adaptation of the dose of drugs in general (Loebstein 1997). Some drugs, such as anticonvulsants and theophylline derivatives, can undergo changes in distribution and elimination, which lead to ineffective treatment because of inadequate drug concentrations in the blood (Lander 1984).

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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