Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants.

Orally administered caffeine and dextromethorphan (DM) were used as pharmacologic probes to determine the effect of infant diet on acquisition of cytochrome P-450 (CYP) enzyme activity during the first 6 mo of life. The caffeine elimination rate constant (ke) was determined from serum, and concentrations of caffeine, DM, and their respective metabolites were measured in urine by high-performance liquid chromatography (HPLC). Caffeine ke was low at 2 wk and displayed a significant positive linear correlation with age (p < 0.

Pharmacokinetics of rifapentine in children.

Background: Rifapentine is a rifamycin antibiotic approved for the treatment of pulmonary infections caused by Mycobacterium tuberculosis. Although the pharmacokinetics of rifapentine has been investigated in adolescents and adults, no studies have assessed the pharmacokinetics of this drug in children or infants.

Methods: Twenty-four children (7.

Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers.

Objective: The effect of lopinavir/ritonavir (LPV/r) administration on cytochrome P450 (CYP) enzyme activity was quantified using a phenotyping biomarker cocktail. Changes in CYP2C9, CYP2C19, CYP3A, CYP1A2, N-acetyltransferase-2 (NAT-2), and xanthine oxidase (XO) activities were evaluated using warfarin (WARF) + vitamin K, omeprazole (OMP), intravenous (IV) and oral (PO) midazolam (MDZ), and caffeine (CAF).

Design: : Open-label, multiple-dose, pharmacokinetic study in healthy volunteers.

Ontogeny of drug metabolizing enzymes in the neonate.

Fetal exposure to xenobiotics is modulated to a considerable degree by the metabolic capabilities of the mother and the placenta. However, once liberated from the uterine environment the neonate is instantly exposed to a wide array of new macromolecules in the form of byproducts of cellular metabolism, dietary constituents, environmental toxins and pharmacologic agents. The rapid and efficient biotransformation of these compounds by Phase I and Phase II drug-metabolizing enzymes is an essential process if the infant is to avoid the accumulation of reactive compounds that could produce cellular injury or tissue dysfunction.