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Pregnancy‐induced changes in the pharmacokinetics of caffeine and its metabolites
Author(s) -
Yu Tian,
Campbell Sarah C.,
Stockmann Chris,
Tak Casey,
Schoen Katherine,
Clark Erin A. S.,
Varner Michael W.,
Spigarelli Michael G.,
Sherwin Catherine M. T.
Publication year - 2016
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.632
Subject(s) - paraxanthine , caffeine , theobromine , theophylline , urine , pharmacokinetics , metabolite , pregnancy , cyp1a2 , medicine , endocrinology , pharmacology , physiology , metabolism , chemistry , biology , genetics , cytochrome p450
This study sought to assess the pharmacokinetic (PK) changes of caffeine and its CYP1A2 metabolites across the 3 trimesters of pregnancy. A prospective, multicenter PK study was conducted among 59 pregnant women (93.2% white) who were studied once during a trimester. One beverage with 30‐95 mg caffeine was consumed, and a blood/urine sample was collected within 1 hour postingestion. Concentrations of caffeine and its primary metabolites were quantified from serum and urine by LC‐MS/MS. There was a significant increase in dose‐normalized caffeine serum and urine concentrations between the first and third trimesters ( P < .05 and P < .01, respectively). Normalized theophylline concentrations also increased significantly in the third trimester in serum ( P < .001) and in urine ( P < .05). The caffeine urine/serum concentration ratio also increased in the last trimester ( P < .05). No significant difference was found in normalized paraxanthine or theobromine concentrations. This study identified decreased caffeine metabolism and an increase in the active metabolite theophylline concentrations during pregnancy, especially in the third trimester, revealing evidence of the large role that pregnancy plays in influencing caffeine metabolism.