Journal of basic and clinical physiology and pharmacology · 2015
Decreased metabolism of 13C-caffeine via hepatic CYP1A2 in marasmus and kwashiorkor based on breath test.
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Oshikoya Kazeem Adeola, Smith Kenneth, Sammons Helen, Choonara Imti
Аннотация
BACKGROUND: Hepatic metabolism of drugs has been rarely studied in children with malnutrition. Caffeine breath test (CBT) has been used to determine the activity of cytochrome P450 1A2 (CYP1A2) enzymes in children. We used the CBT to assess how marasmus and kwashiorkor differentially affect 13C-caffeine metabolism.
METHODS: A total of 45 children composed of 15 children per group of malnutrition (marasmus, marasmic-kwashiorkor, and kwashiorkor) were studied during malnutrition and after nutritional recovery. After an overnight fast, patients ingested 3 mg/kg 13C-caffeine at 0900 h. Duplicate breath samples were collected into an Exetainer bottle at -20, -10, and -1 min and at 15-min intervals for 2 h. The mean cumulative percent dose recovered (CPDR) of 13C-caffeine in the expired 13CO2 was determined over the study period.
RESULTS: The CPDR in the expired 13CO2 in 2 h significantly increased after nutritional recovery in children with marasmus (from 6.80%±3.00% to 7.67%±2.81%; Student's t-test, p=0.001), marasmic-kwashiorkor (from 6.61%±2.26% to 7.56%±2.46%, p=0.041), and kwashiorkor (from 6.29%±1.06% to 7.20%±1.80%, p=0.002). When the three groups of malnutrition were compared, there was no significant difference in their mean CPDR in 2 h during malnutrition [p=0.820, analysis of variance (ANOVA)] and after nutritional recovery (p=0.810, ANOVA).
CONCLUSIONS: Hepatic metabolism of caffeine significantly decreased in children with marasmus, marasmic-kwashiorkor, and kwashiorkor compared to after they had recovered nutritionally. This suggests a decreased CYP1A2 activity in all categories of malnutrition.
METHODS: A total of 45 children composed of 15 children per group of malnutrition (marasmus, marasmic-kwashiorkor, and kwashiorkor) were studied during malnutrition and after nutritional recovery. After an overnight fast, patients ingested 3 mg/kg 13C-caffeine at 0900 h. Duplicate breath samples were collected into an Exetainer bottle at -20, -10, and -1 min and at 15-min intervals for 2 h. The mean cumulative percent dose recovered (CPDR) of 13C-caffeine in the expired 13CO2 was determined over the study period.
RESULTS: The CPDR in the expired 13CO2 in 2 h significantly increased after nutritional recovery in children with marasmus (from 6.80%±3.00% to 7.67%±2.81%; Student's t-test, p=0.001), marasmic-kwashiorkor (from 6.61%±2.26% to 7.56%±2.46%, p=0.041), and kwashiorkor (from 6.29%±1.06% to 7.20%±1.80%, p=0.002). When the three groups of malnutrition were compared, there was no significant difference in their mean CPDR in 2 h during malnutrition [p=0.820, analysis of variance (ANOVA)] and after nutritional recovery (p=0.810, ANOVA).
CONCLUSIONS: Hepatic metabolism of caffeine significantly decreased in children with marasmus, marasmic-kwashiorkor, and kwashiorkor compared to after they had recovered nutritionally. This suggests a decreased CYP1A2 activity in all categories of malnutrition.