title: The pharmacokinetics of caffeine in Nigerian children suffering from malaria and kwashiorkor.
abstract: OBJECTIVE
  Caffeine-containing beverages are generally consumed by Nigerians suffering from malaria and kwashiorkor in the belief that caffeine aids early recovery from these illnesses, which are common in the tropics. However, there are no studies on the influence of these diseases on the absorption and pharmacokinetics of caffeine in Africans.
  
  
  METHODS
  A single oral dose of caffeine was given to five healthy children and to five and seven children suffering from malaria and kwashiorkor, respectively. Caffeine and its dimethylxanthine metabolites were measured in plasma using high-performance liquid chromatography.
  
  
  RESULTS
  The maximum plasma concentration (Cmax) of caffeine and the time of Cmax were similar (P > 0.05) in the three groups. However, the elimination half-life of caffeine was significantly longer in children with malaria (9.2 +/- 3.5 h) (P < 0.01) and kwashiorkor (13.1 +/- 7.9 h) (P < 0.05) than in the healthy controls (3.7 +/- 1.8 h). The total plasma oral clearance of caffeine of 4.4 +/- 1.9 ml/min/kg in healthy children was significantly higher (P < 0.01) than in those with kwashiorkor (2.0 +/- 0.9 ml/min/kg) and malaria (1.6 +/- 1.0 ml/min/ kg) (P < 0.05). Paraxanthine was the principal metabolite in all the three groups with Cmax significantly higher in healthy children (1.3 +/- 0.3 microg/ml) than in children with malaria (0.8 +/- 0.4 microg/ml) (P < 0.05) and kwashiorkor (0.3 +/- 0.1 microg/ml) (P < 0.0001). CYP1A2 activity, measured by the plasma ratios of paraxanthine: caffeine, was significantly lower in kwashiorkor and malaria.
  
  
  CONCLUSIONS
  This study showed that the plasma kinetics of caffeine are significantly altered in malaria and kwashiorkor, and CYP1A2 activity was lower in these two disease groups.
authors.affiliation: Clinical Pharmacology Group, Southampton, United Kingdom. asegun@hotmail.com
authors.forename: O O
authors.initials: OO
authors.lastname: Akinyinka
authors.forename: A
authors.initials: A
authors.lastname: Sowunmi
authors.forename: R
authors.initials: R
authors.lastname: Honeywell
authors.forename: A G
authors.initials: AG
authors.lastname: Renwick
mesh_terms: D000284:Administration, Oral; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007732:Kwashiorkor / Q000097:blood / Q000378:metabolism*; D008288:Malaria / Q000097:blood / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009549:Nigeria; D013806:Theophylline / Q000378:metabolism
chemical_list: D002110:Caffeine; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2; C021183:1,7-dimethylxanthine