Increased theophylline metabolism in the menstrual phase of healthy women,☆☆,

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Abstract

Background: We previously reported on a Japanese woman with premenstrual asthma whose serum theophylline concentration was lower before the onset of her menstrual period. We evaluated the clearance of theophylline in each phase of her menstrual cycle and found an increase in clearance in the premenstrual and menstrual phases. Objective: This study was designed to investigate whether changes in theophylline clearance may occur with the menstrual cycle in nonasthmatic women. Methods: Aminophylline, 250 mg, was infused intravenously for 45 minutes, and the clearance of theophylline was calculated in seven healthy, ovulatory women on days 1 or 2, 10, and 20 or 25 of the menstrual cycle. The serum concentration of theophylline was determined with an enzyme immunoassay (homogeneous). Results: Theophylline clearance was significantly higher and its half-life was significantly shorter in the menstrual phase than in the follicular phase. Conclusion: The metabolism of theophylline, and consequently, its clearance were increased in healthy women around the onset of menses. Clinicians must therefore consider the menstrual variation in theophylline metabolism when prescribing this drug to female patients. (J Allergy Clin Immunol 1997;100:39-43.)

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Subjects

Seven healthy, ovulatory Japanese women aged 30 to 44 years (mean age, 34.9 years) were investigated. No subject had asthma, and none of them had received theophylline previously. They recorded their basal body temperature during the 1-month study. All subjects gave their informed consent to participate in this study.

Sampling

Blood samples were collected after 30 minutes of bed rest and before breakfast on the day of onset or day 2 of menses, day 10, and day 20 or 25. These sampling times corresponded

Menstrual cycle

All subjects showed a biphasic pattern of basal body temperature and an increase in progesterone level in the luteal phase, indicating that they were in the ovulatory cycle. A normal pattern of change was seen in the estrogen and progesterone levels for all subjects (Table I).

. Serum levels of estradiol and progesterone in seven subjects

PhaseEstradiol (pg/ml)Progesterone (ng/ml)
Follicular80.7 ± 44.20.26 ± 0.14
Luteal154.4 ± 123.113.17 ± 5.23
Menstrual22.8 ± 12.60.46 ± 0.24

Values are expressed as

Discussion

In our previous study of a woman with asthma, theophylline clearance was higher, and the half-life was shorter in the premenstrual and menstrual phases.1 In this study of healthy nonasthmatic women, theophylline clearance was significantly higher in the menstrual phase than in the follicular phase, and the half-life was shorter in the menstrual phase than in the follicular phase. These results are compatible with those in our previous report.

Diet and activity are significant factors for

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From aThe Third Department of Internal Medicine and bHealth Science Center of Tottori University Faculty of Medicine, Yonago, Japan.

☆☆

Reprint requests: Keiko Nagata, MD, The Third Department of Internal Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Machi Yonago, 683, Japan.

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