Developmental changes in hepatic esterase activity towards chloramphenicol succinate and its Michaelis-Menten constant of liver, kidney and lung in human
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Hepatic esterase activity toward chloramphenicol succinate shows significant postnatal development. Enzyme activity and Vmax values increase with age, indicating the liver
Area of Science:
- Pharmacology
- Biochemistry
- Human Physiology
Background:
- Chloramphenicol succinate is a prodrug requiring hydrolysis for activation.
- Esterase enzymes are crucial for drug metabolism, but their developmental profiles are not fully understood.
Purpose of the Study:
- To investigate the developmental changes in hepatic esterase activity towards chloramphenicol succinate in humans.
- To compare esterase activity across different human age groups and organs.
Main Methods:
- Human tissue samples were collected from fetuses, neonates, infants, and adults.
- Hepatic esterase activity was measured using chloramphenicol succinate as a substrate.
- Kinetic parameters (Km and Vmax) were determined for liver, lung, and kidney tissues.
Main Results:
- Esterase activity was significantly lower in fetal and neonatal tissues compared to infants and adults.
- Km values were consistent across age groups within each organ but varied between organs (renal Km higher).
- Vmax values demonstrated a clear developmental increase in all investigated organs.
Conclusions:
- Hepatic esterase activity towards chloramphenicol succinate exhibits significant postnatal development.
- The liver plays a primary role in chloramphenicol succinate hydrolysis, especially considering its weight.
- Understanding these developmental changes is crucial for optimizing chloramphenicol-based therapies in pediatric populations.
Abstract:
The hepatic esterase activities towards chloramphenicol succinate were determined in the tissues from 45 human subjects, including 18 electively aborted fetuses, 5 premature and 8 full-term newborn babies, 8 infants and 6 adults. The enzyme activities in the tissues from the fetuses and neonates were significantly lower compared with those obtained from the infants and adults. This suggests that the activity showed postnatal development. Kinetic studies of the esterase activity revealed that hepatic Km values were similar to those of the lung, but renal Km values were about 3 times higher than those of the liver and lung. In each organ, no age-related changes in Km values were observed. However, all the Vmax values in each organ showed developmental increases. Therefore, the liver plays the most important role in hydrolysis of chloramphenicol succinate when the weight of the organ is taken into consideration.