Effect of age on pharmacokinetics

Pharmacokinetics in the embryonic period and in newborns

In the early stages of development, drug metabolism is significantly impaired. This is directly related to the status of hepatic enzyme systems, which undergo a long process of physiological maturation.

• Embryonic period: During embryogenesis, most of the enzymes required for biotransformation are completely absent in the fetus. This makes the embryo extremely vulnerable to any xenobiotics crossing the placenta.
• First weeks of life: In newborns (during the first 2–4 weeks), enzyme activity remains critically low. Phase II metabolism—conjugation reactions—is particularly affected.
• Normalization period: Gradual maturation of biotransformation systems and stabilization of enzyme activity levels occur only between 1 and 6 months of a child's life.

The clinical significance of these features is immense. Due to the inability of the newborn's organism to effectively metabolize and bind drugs, there is a high risk of toxicity. A prime example is the antibiotic chloramphenicol (Chloramphenicolum). Its use in the first weeks of life is strictly contraindicated: due to glucuronyl transferase deficiency, conjugation processes are impaired, leading to the dangerous accumulation of the drug's toxic metabolite in the infant's tissues.

Pharmacokinetic changes in advanced and old age

Patients over 60 years of age are characterized by the decline of many physiological functions, which directly affects the pharmacokinetics of administered drugs. The aging process affects both cellular and organ levels.

There are four key physiological changes that influence the fate of a drug in the elderly body:

1. Decreased activity of hepatic microsomal enzymes. The ability of hepatocytes to oxidize and transform drug molecules drops significantly.
2. Reduction of hepatic parenchymal mass. The actual volume of functioning tissue responsible for xenobiotic detoxification is reduced.
3. Decreased hepatic blood flow. Reduced organ perfusion results in slower delivery of drugs to enzyme systems.
4. Decreased protein synthesis. A deficiency of plasma transport proteins (primarily albumins) critically affects the distribution of drugs, as the free (active) fraction of the drug in the blood increases.

The main pharmacokinetic consequence of all these physiological shifts is a pronounced slowdown in metabolism. Drugs circulate in the body longer, creating a serious risk of cumulation.

Clinical tactics and dosing

Understanding age-related characteristics dictates strict rules for the physician in choosing the dosing regimen.

Since patients over 60 have slower metabolism and a high risk of cumulation, standard therapeutic doses become excessive and potentially toxic for them. The primary safety strategy in geriatric pharmacology is prescribing drugs in reduced doses. This is the only way to compensate for the physiological decrease in enzyme activity, reduction in liver mass, and decline in hepatic blood flow, ensuring effective and safe treatment.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of conjugation reactions in the liver
• Role and functions of glucuronyl transferase
• Microsomal enzymes: cytochrome P450
• The relationship between protein synthesis and drug distribution
• The concept of drug cumulation

Other topics in "General Pharmacology"

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