Objectives: To compare caffeine pharmacokinetics (200 mg single oral dose) between obese and lean subjects and in obese subjects prior to and following weight reduction. In the obese group antipyrine (1000 mg single 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/m2), referred from the outpatient metabolic clinic and 14 lean (Group B) subjects participated in the study. Weight (mean +/- 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 38.5 +/- 5.8 vs 22.6 +/- 1.7 kg/m2 respectively, P < 0.001).

Interventions: Single dose oral administration of caffeine (200 mg) and antipyrine (1000 mg) in Group A and only caffeine in Group B. Twice single dose 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 concentrations-time curves.

Results: Caffeine elimination half-life (T1/2) and clearance (CLo) 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 Varea 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 Varea were similar (48.3 +/- 11.4 vs 49.9 +/- 9.3 L respectively, P > 0.3). Caffeine T1/2 and CLo were not significantly altered by the 30.2 +/- 12.3 kg weight loss obtained in Group C subjects, but caffeine Varea was significantly reduced (55.6 +/- 9.3 L before, 47.8 +/- 9.5 L after, P < 0.04) and Varea corrected for body weight was significantly increased (0.46 +/- 0.03 L/kg before, 0.52 +/- 0.05 L/kg after, P < 0.05).

Conclusions: Caffeine pharmacokinetics are only minimally altered by obesity. The use of caffeine containing drugs in obese subjects does not necessitate significant dosage modification.