title: Pregnancy-induced changes in the pharmacokinetics of caffeine and its metabolites.
abstract: 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.
authors.affiliation: Division of Clinical Pharmacology, School of Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Yu
authors.affiliation: Division of Clinical Pharmacology, School of Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Campbell
authors.affiliation: Division of Clinical Pharmacology, School of Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.affiliation: Clinical Trials Office, Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Tak
authors.affiliation: Division of Clinical Pharmacology, School of Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Schoen
authors.affiliation: Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, School of Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Erin A S
authors.initials: EA
authors.lastname: Clark
authors.affiliation: Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, School of Medicine, University of Utah, Salt Lake City, UT, USA.|Intermountain Healthcare, Women and Newborns Clinical Programs, Salt Lake City, Utah, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Varner
authors.affiliation: Division of Clinical Pharmacology, School of Medicine, University of Utah, Salt Lake City, UT, USA.|Clinical Trials Office, Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
authors.affiliation: Division of Clinical Pharmacology, School of Medicine, University of Utah, Salt Lake City, UT, USA.|Clinical Trials Office, Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
mesh_terms: D000328:Adult; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005260:Female; D006801:Humans; D011247:Pregnancy / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011264:Pregnancy Trimesters / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013805:Theobromine / Q000097:blood; D013806:Theophylline / Q000097:blood; D055815:Young Adult
chemical_list: D002110:Caffeine; D013806:Theophylline; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D013805:Theobromine; C021183:1,7-dimethylxanthine
keywords: caffeine; metabolites; pharmacokinetics; pregnancy