Comparative study of rifampicin pharmacokinetics administered orally and intravenously in the fasted and non-fasted rats

Effect of food on the absorption characteristics of oral rifampicin was studied in the fasted rats. Rifampicin dissolved in a new cosolvent was also injected to the rats intravenously, and the pharmacokinetic analysis was performed to explain the effect of food on the gastrointestinal absorption of rifampicin. Rifampicin was absorbed rapidly and completely in the fasting state. Food had a profound effect on the gastrointestinal absorption of rifampicin, i.e., bioavailability and the extent of absorption were decreased to less than one-third of the fasting state in the postprandial state. Food seemed to inhibit the absorption and reabsorption of rifampicin in the gastrointestinal tract, but not the absorption rate constant. Hepatobiliary excretion seemed to be the major route of elimination, since the renal clearance accounted for only 8% of the systemic clearance. Nevertheless, first-pass effect was negligibly small and most of rifampicin absorbed could reach systemic circulation. Serum concentration change of oral rifampicin on multiple dosing differed markedly in the fasting and postprandial state, which suggested the need of careful adjustment of dosage regimen in both states.