The effect of the menstrual cycle on the pharmacokinetics of caffeine in normal, healthy eumenorrheic females
Abstract
Objective Hormonal fluctuations of estrogen and progesterone in eumenorrheic women may be capable of altering the pharmacokinetics of certain agents. The objective of this study was to determine the effect of the luteal, ovulatory and follicular phases of the menstrual cycle on the pharmacokinetics of caffeine, a low clearance, flow-independent drug.Methods Subjects were ten healthy, non-smoking, eumenorrheic females who were not pregnant and had not used oral contraceptives for a minimum of 3 months prior to the study. Blood samples were collected during one menstrual cycle for the determination of estradiol and progesterone concentrations during the follicular (days 2-6 post-onset of menses), ovulatory (days 13-16 post-onset of menses) and luteal (days 22-26 post-onset of menses) phases. Caffeine was administered over a single menstrual cycle during the follicular, ovulatory and luteal phases. Each subject was administered a single oral dose of caffeine (300 mg) in 100 ml of lemonade during each phase of the menstrual cycle. A venous catheter was used to collect blood samples at pre-dose and at the following time points: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 and 24 h. Plasma caffeine concentrations were determined using a validated ultraviolet high-performance liquid chromatography method.Results There were no significant (P < 0.05) differences in the pharmacokinetic parameters of caffeine across the menstrual cycle phases. The average area under the plasma concentration-time curve (AUCinf) was 93.01 mg 1(-1) x h and the absorption rate constant (ka) was 2.88 h(-1) during the ovulatory phase, 83.0 mg 1(-1) h and 2.06 h(-1), respectively, during the luteal phase and 84.7 mg 1(-1) x h and 1.84 h(-1), respectively, during the follicular phase.Conclusions These findings suggest that the menstrual cycle does not significantly alter the pharmacokinetics of caffeine.
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Studies have not found marked differences in caffeine metabolism between the luteal and follicular phases of the menstrual cycle.
“However, studies have not found marked differences in caffeine metabolism between the luteal and follicular phases of the menstrual cycle (57, 58).”
From The Safety of Ingested Caffeine: A Comprehensive Review (2017) · cites this paper as [58]
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- Authors
- Kamimori, G. H., Joubert, A., Otterstetter, R., Santaromana, M., & Eddington, N. D.
- Affiliations
- University of Maryland, Baltimore (US)
- Walter Reed Army Institute of Research (US)
- ORCID
- Otterstetter, R.
- Venue
- European Journal of Clinical Pharmacology
- Published
- 1999-08-09
- Volume
- 55
- Issue
- 6
- Pages
- 445-449
- ISSN
- 0031-6970 (ISSN-L)
- 1432-1041
- OpenAlex
- W2024743624
- Cited by
- 49
- References
- 14
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 1 · 2022: 3 · 2021: 2 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 2 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- U.S. Army Medical Research and Development Command
- Topics
- Health Sciences › Medicine › Pharmacology › Coffee research and impacts
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- caffeine, menstrual cycle, pharmacokinetics, estrogen, progesterone, follicular phase, ovulatory phase, luteal phase, estradiol, plasma caffeine concentration, drug clearance, healthy women
- MeSH terms
- Adult, Central Nervous System Stimulants, Caffeine, Female, Follicular Phase, Humans, Luteal Phase, Menstrual Cycle, Ovulation, Cross-Over Studies
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