CAFFEINE PHARMACOKINETICS IN OBESITY AND FOLLOWING SIGNIFICANT WEIGHT-REDUCTION

OBJECTIVES: To compare caffeine pharmacokinetics (200 mg single oral d ose) between obese and lean subjects and in obese subjects prior to an d following weight reduction. In the obese group antipyrine (1000 mg s ingle oral dose) pharmacokinetics were also evaluated one week before caffeine administration. SETTING: Teaching university hospital. DESIGN : Single dose, open study. SUBJECTS: Twenty obese subjects (Group A) ( BMI exceeding 30 kg/m(2)), referred from the outpatient metabolic clin ic and 14 lean (Group B) subjects participated in the study. Weight (m ean +/- s.d.) and BMI were significantly greater in the obese than the lean subjects (110.4 +/- 19.2 vs 66.9 +/- 13.3 kg respectively, and 3 8.5 +/- 5.8 vs 22.6 +/- 1.7 kg/m(2) respectively, P < 0.001). INTERVEN TIONS: Single dose oral administration of caffeine (200 mg) and antipy rine (1000 mg) in Group A and only caffeine in Group B. Twice single d ose oral administrations of caffeine (200 mg) in six subjects (Group C ), prior to and following weight loss. MAIN OUTCOME MEASURES: Caffeine and antipyrine pharmacokinetics were derived from the plasma concentr ations-time curves. RESULTS: Caffeine elimination half-life (T1/2) and clearance (CL(0)) were similar in obese and lean subjects (6.54 +/- 2 .85 vs 6.08 +/- 2.23 h respectively and 100.7 +/- 49.5 vs 82.6 +/- 34. 0 ml/min respectively, P <0.05). Caffeine V-area was greater in group A than in Group B (48.3 +/- 11.4 vs 40.1 +/- 13.0 L respectively, P = 0.06) but when corrected for body weight significantly reduced values were obtained in the obese group (0.44 +/- 0.06 vs 0.59 +/- 0.10 L/kg respectively, P < 0.001). In group A subjects caffeine and antipyrine V-area were similar (48.3 +/- 11.4 vs 49.9 +/- 9.3 L respectively, P > 0.3). Caffeine T,,, and CL, were not significantly altered by the 30. 2 +/- 12.3 kg weight loss obtained in Group C subjects, but caffeine V -area was significantly reduced (55.6 +/- 9.3 L before, 47.8 +/- 9.5 L after, P < 0.04) and V-area corrected for body weight was significant ly increased (0.46 +/- 0.03 L/kg before, 0.52 +/- 0.05 L/kg after, P < 0.05). CONCLUSIONS: Caffeine pharmacokinetics are only minimally alte red by obesity. The use of caffeine containing drugs in obese subjects does not necessitate significant dosage modification.