Pharmacokinetics in the Embryonic Period and Neonates
At early stages of development, drug metabolism is significantly impaired. This is directly related to the status of hepatic enzyme systems, which undergo a prolonged path of physiological maturation.
- Embryonic period: During embryogenesis, most enzymes required for biotransformation are completely absent in the fetus. This makes the embryo highly vulnerable to any xenobiotics crossing the placenta.
- First weeks of life: In neonates (the first 2–4 weeks), enzyme activity remains critically low. Phase II metabolism—conjugation reactions—is especially deficient.
- Normalization period: Gradual maturation of biotransformation systems and stabilization of enzyme activity occurs only between 1 and 6 months of age.
The clinical significance of these features is immense. Due to the inability of the neonatal body to effectively metabolize and conjugate drugs, there is a high risk of toxicity. A striking example is the antibiotic chloramphenicol (Chloramphenicolum). Its use in the first weeks of life is strictly contraindicated: due to a deficiency of the enzyme glucuronyl transferase, conjugation is impaired, leading to dangerous accumulation of the toxic drug metabolite in infant tissues.
Pharmacokinetic Changes in Elderly and Senile Age
Patients over 60 years old experience a decline in many physiological functions, which directly affects the pharmacokinetics of administered drugs. The aging process affects both cellular and organ levels.
Four key physiological changes affect the fate of a drug in the elderly body:
- Decreased activity of hepatic microsomal enzymes. The ability of hepatocytes to oxidize and transform drug molecules drops noticeably.
- Reduced hepatic parenchymal mass. The actual volume of functioning tissue responsible for xenobiotic detoxification shrinks.
- Decreased hepatic blood flow. Reduced organ perfusion means that drugs are delivered more slowly to enzyme systems.
- Decreased protein synthesis. A deficiency in plasma transport proteins (primarily albumins) critically affects drug distribution because 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 Strategy and Dosing
Understanding age-related characteristics dictates strict rules for selecting dosing regimens in clinical practice.
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 medications in reduced doses. This is the only way to compensate for the physiological decline in enzyme activity, reduced liver mass, and decreased hepatic blood flow, thereby ensuring effective and safe treatment.