Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives

Abstract

The effect of chronic (greater than 3 months) administration of low-dose oestrogen-containing (less than 50 micrograms oestrogen) oral contraceptives (OCS) on the pharmacokinetics of caffeine has been examined in a treated females matched with 9 non-smoking, drug-free, healthy control females of similar age, weight and ethnic origin. Each subject received 162 mg caffeine base orally after an overnight fast. OCS subjects had a prolonged elimination half-life of caffeine, (mean 7.88 h vs 5.37 h in the controls). This was the result of marked impairment of the plasma clearance of caffeine (1.05 vs 1.75 ml/min/kg, respectively) with no change in apparent volume of distribution (0.685 in OCS vs 0.7501/kg in the control group). The absorption parameters determined were peak plasma caffeine concentration (3.99 vs 4.09 micrograms/ml) and time to peak concentration after drug administration (1.52 vs 0.79), which was moderately prolonged in OCS users. Thus, caffeine clearance, previously reported to be a specific marker of cytochrome P-448 activity in man, is decreased by chronic OCS use. This suggests that OCS may cause significant impairment of this enzyme activity as assessed in vivo. With chronic caffeine consumption, OCS users are predicted to have an increased steady-state plasma caffeine concentration as compared to non-OCS users.

Caffeine Ingestion Decreases Glucose Disposal During a Hyperinsulinemic-Euglycemic Clamp in Sedentary Humans

“…Menstrual position, oral contraceptive use, pregnancy, and menopause are all conditions that can affect caffeine metabolism (28,29), carbohydrate management, and insulin sensitivity (30). Furthermore, estrogen has been reported to inhibit caffeine metabolism and the pharmacokinetics of caffeine.…”

Effect of Caffeine on Fatigue During Submaximal Isometric Contractions at Different Knee Angles

“…A number of selection criteria were used to control for factors known to modify caffeine metabolism. Males were recruited, as the use of oral contraceptives can augment the half-life of caffeine [19], and throughout the luteal phase of the menstrual cycle caffeine clearance can be reduced [20]. Subjects were non-smokers, as nicotine can adjust the rate of caffeine degradation [21].…”

Prenatal Caffeine Assessment: Fetal and Maternal Biomarkers or Self-Reported Intake?

“…Fetal exposure to caffeine depends not only on maternal consumption, but on the rate at which caffeine is metabolized by the mother and cleared from the fetal circulation. Numerous endogenous and exogenous factors influence caffeine metabolism, including cigarette smoking (4)(5)(6), pregnancy (4), oral contraceptive use (7,8), liver disorders (9), and certain medications (10). Cigarette smoking nearly doubles the rate of caffeine metabolism due to the enzyme-inducing effects of polycyclic aromatic hydrocarbons, known to increase liver enzyme activity (4)(5)(6).…”