Metabolism of omeprazole after two oral doses in children 1 to 9 months old.
Proton pump inhibitors (PPIs) have been used recently for gastrointestinal esophageal reflux disease (GERD) in children older than one year with good results. However, the pharmacokinetics of PPIs have not been studied in children less than two years old. The aim of our study was to evaluate the frequency of the main phenotypes of the metabolizing enzymes CYP2C19 and CYP3A4 in Mexican infants. Our results indicate no significant difference between the 0.5 and the 1.5 mg/kg doses. The percentage of CYP2C19-poor metabolizers was 17% in babies below 4 months and was not detected in children above 3 months. When a combined CYP2C19- and CYP3A4- phenotype was estimated, omeprazole levels were significantly higher in poor metabolizers than in extended metabolizers. The percentage of ultra-extensive metabolizers in children older than 3 months were 20% and 33% for CYP2C19 and CYP3A4 respectively, compared to only 6% and 9% respectively, in babies between 1 and 3 months old. In general children, under 4 months had higher omeprazole levels and an immature metabolism. Studies in children older than 2 years old have showed similar pharmacokinetics to adults. For children between 1 month old and up to 9 months, we suggest the use of the 0.5 mg/kg dose, since it prevents accumulation in poor metabolizers, caution is recommended to identify ultra-fast metabolizers, but this would require new studies.
Hoyo-Vadillo
Carlos
C
Div. Pharmacology, Cinvestav, Mexico City. carlosh@cinvestav.mx
Venturelli
Caterina R
CR
González
Hector
H
Romero
Elba
E
Cervantes
Roberto
R
Mata
Norberto
N
Ortiz
Ana Carolina
AC
Rincón
Victor
V
Zarate
Flora
F
Sosa
Cristina
C
Ramírez-Mayans
Jaime
J
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008800:Mexico / Q000453:epidemiology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D010641:Phenotype
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; C040450:omeprazole sulfone; D003577:Cytochrome P-450 Enzyme System; C049963:5-hydroxymethylomeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C104464:CYP3A protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009853:Omeprazole