EFFECTS OF TIMING OF FOOD AND FLUID VOLUME ON CEFETAMET PIVOXIL ABSORPTION IN HEALTHY NORMAL VOLUNTEERS

Cefetamet pivoxil (1,000 mg orally) absorption was evaluated in 16 male subjects (age, 23.4 ± 1.7 years; weight, 73.9 ± 7.0 kg) 1 h before (BE), with (WI), and 1 h after (AF) a standard breakfast. The time to peak concentration of cefetamet in plasma (T(max)) was increased from 3.25 ± 1.44 h in the BE group to 4.31 ± 1.54 and 4.13 ± 1.54 h in the WI and AF groups, respectively (P < 0.05). The maximum cefetamet concentration in plasma (C(max)) and the area under the plasma cefetamet concentration-time profiles (AUC) in the BE, WI, and AF groups were 5.50 ± 1.06, 5,47 ± 1.4, and 6.57 ± 0.93 μg/ml and 38.2 ± 10.0, 35.7 ± 11.9, and 42.8 ± 6.8 μg · h/ml, respectively. The C(max) and AUC values were not different between the BE and WI groups (P > 0.05). However, differences in these values were found between the WI and AF groups (P < 0.05). The effect of fluid volume intake on cefetamet pivoxil (1,000 mg orally) absorption was evaluated in 12 male subjects (age, 23.8 ± 2.3 years; weight, 74.9 ± 9.0 kg) under fasted and WI conditions. Increasing fluid volume intake from 250 to 450 ml under the fasted condition had no effect on the absorption of the prodrug (T(max), 2.50 ± 0.52 versus 2.83 ± 0.94 h; C(max), 4.89 ± 1.04 versus 4.84 ± 0.89 μg/ml; AUC, 29.6 ± 5.1 versus 30.7 ± 7.1 μg · h/ml; P > 0.05). Similar results were obtained under the fed state (T(max), 4.75 ± 0.62 versus 4.67 ± 0.78 h; C(max), 6.00 ± 1.37 versus 6.36 ± 1.14 μg/ml; AUC, 38.6 ± 8.8 versus 39.6 ± 6.1 μg · h/ml; P > 0.05). Thus, independent of fluid volume intake, cefetamet pivoxil absorption is enhanced when it is given within 1 h of a meal, and it is recommended that the prodrug should be taken during this period of increased bioavailability.