Factors affecting aminoglycoside disposition: effects of circadian rhythm and dietary protein intake on gentamicin pharmacokinetics.

The effects of dietary protein loading and circadian cycle on the pharmacokinetics of gentamicin were studied in healthy adult men. Ten subjects fasted overnight, and at 8 AM the next morning they received gentamicin, 1.5 mg/kg. Serum and urine samples were obtained over a 6-hour period. In two additional clearance studies with 2-week washout periods in between, 10 subjects were given the same dose of gentamicin at 8 PM in the fasted state and six subjects were also studied in a protein-supplemented (90 gm) state. Pharmacokinetic analysis revealed no significant effect of circadian cycle on gentamicin pharmacokinetic parameters at each of the two fasted periods. In contrast, dietary protein loading resulted in a significant decrease in the elimination t1/2 (P less than 0.05) and an increase in total body clearance compared with the fasted 8 PM study. Urinary excretion of gentamicin was also found to increase significantly (P = 0.03) as a result of protein intake compared with the fasted evening study period. Our study demonstrates the importance of dietary controls in chronopharmacokinetic studies of drugs eliminated predominantly by renal mechanisms.