Decreased metabolism of 13C-caffeine via hepatic CYP1A2 in marasmus and kwashiorkor based on breath test

Kazeem Adeola Oshikoya; Kenneth Smith; Helen Sammons; Imti Choonara

doi:10.1515/jbcpp-2013-0081

Article

Decreased metabolism of ¹³C-caffeine via hepatic CYP1A2 in marasmus and kwashiorkor based on breath test

Kazeem Adeola Oshikoya , Kenneth Smith , Helen Sammons and Imti Choonara

Published/Copyright: October 11, 2013

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 26 Issue 1

Abstract

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.

Keywords: 13C-caffeine; children; CYP1A2 enzyme; drug metabolism; kwashiorkor; marasmus

Corresponding author: Dr. Kazeem Adeola Oshikoya, Academic Division of Child Health, Medical School in Derby, University of Nottingham, Royal Derby Hospital, Uttoxeter Road, Derby DE22 3DT, UK, Phone: +44-796-128-4468, E-mail: kazeeoshikoya@ymail.com; and Pharmacology Department, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria

Acknowledgments

The authors appreciate the cooperation of the parents and the children who participated in the study. The hospital staff that assisted in recruiting and feeding the patients is also appreciated.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2013-6-17

Accepted: 2013-8-14

Published Online: 2013-10-11

Published in Print: 2015-1-1

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2013-0081

Keywords for this article

13C-caffeine; children; CYP1A2 enzyme; drug metabolism; kwashiorkor; marasmus