Relationship between Maternal Progesterones and the Delayed Drug Metabolism in the Neonate

Kardish, R.; Feuer, G.

doi:10.1159/000240446

Cited by 30 publications

(4 citation statements)

References 19 publications

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“…However, in the relatively crude enzyme fraction used in this project, a change in the apparent K, could be interpreted in a number of different ways, in addition to a change in the enzyme itself. If inhibitor substances are present during the perinatal period (26,27), they could conceivably be competing in the assays with the added substrates. Soyka and Long (27) reported that pregnanolone ( l e 7 M ) acts as a competitive inhibitor of the 0-demethylation of g-nitroanisole in the rat.…”

Section: Discussionmentioning

confidence: 99%

The Development of Kinetic Parameters of Hepatic Drug-Metabolizing Enzymes in Perinatal Rats

Bell¹,

Ecobichon²

1975

Can. J. Biochem.

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The development of the apparent kinetic parameters K- m and V-max was studied in perinatal Wistar rats for three functionally diverse, hepatic enzymes (p-nitroanisole O-demethylase, carboxylesterase and bromosulphophthalein-glutathione conjugating enzyme), the period studied being from 3 days prepatum to 35 days postpartum. The kinetic parameters underwent marked quantitative changes during development, which appeared to be independent of sex for the first 5 weeks postpartum.

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Section: Discussionmentioning

confidence: 99%

The Development of Kinetic Parameters of Hepatic Drug-Metabolizing Enzymes in Perinatal Rats

Bell¹,

Ecobichon²

1975

Can. J. Biochem.

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“…1964: Vest, 1965Liscio. 1969: Wilson, 1970;Kardish and Feuer. 1972;Sereni et aI., 1973a;1973b;Morselli et al .. 1974;KJinger , 1976).…”

Section: Biotransformation and Apparent Plasma Half-lifeunclassified

Clinical Pharmacokinetics in Neonates

Morselli

1976

Clinical Pharmacokinetics

159

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Recent concern over toxic effects of drugs in newborns, infants and children have stressed the need for better knowledge of drug kinetics during development. The present review focuses on the available data on clinical pharmacokientics in the neonate. Despite the lack of systematic approaches on drug disposition during the first month of life, the body of data currently available indicates profound differences in drug disposition between neonates and older infants, children and adults. In terms of physiological and anatomical factors the neonate has to be considered as a 'unique drug recipient'. For all the specific variables which govern the drug kinetic pattern (absorption, blood esterase activity, plasma protein binding, metabolic degradation and renal excretion), there are clear difference between neonates and older infants and children. Such differences are not always unidirectional. In the case of absorption, they depend on the maturational stage, but more on the physico-chemical properties of the individual compound. Esterase activiy and renal excretion are also related to the physico-chemical properties of the drug, but are more clearly linked with the development stage. Plasma protein blinding is generally reduced, and depends on several factors, not all of which are as yet clearly identified and understood. Biotransformation activities are usually very low, but may be increased several-fold by exposure to inducing agents. Hydroxylating activity and conjugation with glucronic acid appear to be the two metabolic pathways which are most defective at birth, while sulphate and gylcine conjugation, and dealkylation activities are close to the adult pattern. The material reviewed is fragmentary and does not always permit a comparison of the data obtained in newborns with those reported for adults. Differences in the methodology used and in the kinetic criteria further complicate the matter. It is, however, clearly emerging that drug disposition may vary greatly in the newborn in relation to its developmental age. The reported differences may be relevant for clinical practice and stress the need for more detailed information on drug kinetics in the neonate. Such information may be achieved by carefully planned clinical trials, but more meaningfully, and more profitably for the individual patient, by a very carefully, well integrated monitoring of the neonate a risk. By such an approach, where drug plasma levels are related to drug effects and to the pathophysiological condition, the significance of various factors on drug disportion during development will be better clarified, thus allowing a more rational and safer therapy in the newborn.

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“…Interest has focused primarily on the effects of certain steroids and phospholipids (see above). Particularly, metabolites of progesterone that are present in the plasma of pregnant women and fetuses (86) are potent inhibitors of conjugative (183) and oxidative (87)(88)(89) enzymes. Endoge nous ligands have been implicated to some extent also in explanations of the peri nate's decreased plasma protein binding capacity (184, 185).…”

Section: Regulatory Mechanismsmentioning

confidence: 99%