Abstract
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.
Similar content being viewed by others
Literature Cited
Cricchio, R., Arioli, V. and Lancini, G.C.: Hydrazones of 3-fomyl ryfamycin SV. Hydrazone with N-amino-N′-substituted piperazines: synthesis, antibacterial activity and other biological properties.II. Farmaco. Ed. Sc.,30, 605 (1975).
Birmingham, A.T., Coleman, A.J., Orme, M.L. E., Park, B.K., Pearson, N.J., Short, A.H. and Southgate, P.J.: Antibacterial activity in serum and urine following oral administration in man of DL 473 (a cyclopentyl derivative of rifampicin).Proceedings of the BPS.13th, 15th, 455 (1973).
Arioli, V., Berti, M., Carniti, G., Randisi, E., Rossi, E. and Scotti, R.: Antibacterial activity of DL 473, a new semisynthetic rifamycin derivative.J. Antibiot.,34, 1026 (1981).
Acocella, G., Segre, G., Ponti, R., Pagani, V., Pallanza, R., Perna, G. and Simon, P.. Pharmacokinetic study on intravenous rifampicin in man.Pharmacol, Res. Comm.,16, 723 (1984).
Acocella, G., Mattiussi, R. and Segre, R.: Multi compartmental analysis of serum, urine, and bile concentrations of rifampicin and desacetyl rifampicin in subjects treated for one week.Pharmacol. Res. Comm.,10, 271 (1978).
Polasa, K. and Krishnaswamy, K.: Effect of food on bioavailability of rifampicin.J. Clin. Pharmacol.,23, 433 (1983).
Hanano, M.et al.:Drug Disposition in the Body (Japanese) p. 47 (1981).
Yamaoka, K., Nakagawa, T. and Uno T: Application of Akaike’s information criterion (AIC) in the evaluation of linear pharmacokinetic equations.J. Pharmacokin. Biopharm.,6, 165 (1978).
Newton, D.W.: Physicochemical determinations of incompatibility and instability of drugs for injection and infusion.Handbook on Injectable Drugs. 3rd edition, American Society of Hospital Pharmacists, Ind., XI (1983).
Kim, C.K. and Shin, H.J.: Soluble complex formation of rifampicin with arginine.Yakhak Hoeji 27, 11 (1983).
Assandri, A., Ratti, B. and Cristina, T.: Pharmacokinetics of rifapentine, a new long lasting rifamycin, in the rat, the mouse and the rabbit.J. Antibiot.,39, 1066 (1984).
Vlasakova, V., Benes, J. and Zivny, K.: Analysis of rifampicin and of its hydrogenated derivatives by high-performance liquid chromatography.J. Chromalog.,151, 199 (1978).
Guillaumont, M., Leclercq, M., Frobert, Y., Guise, B. and Harf, R.: Determination of rifampicin, desacetyl rifampicin, isoniazid and acetyl isoniazid by high-performance liquid chromatography; Application to human serum extracts, polymorphonudeocytes and alveolar macrophages.J. Chromatog.,232, 369 (1982).
Lecaillon, J.B., Febvre, N., Metayer, J.P. and Souppart, C.: Quantitative assay of rifampicin and three of its metabolites in human plasma, urine and saliva by high-performance liquid chromatograph.J. Chromatog.,145, 319 (1978).
Shimizuet al.: Biotransformation of rifampicin (Japanese), 969.
Holdiness, M.R.: Clinical pharmacokinetics of the antituberclosis drugs.Clin. Pharmacokin.,9, 511 (1984).
Nagasakiet al.: Study on the absorption, excretion and distribution of rifampicin (Japanese), 961.
Siegler, D.I., Bayant, M., Burley, D.M., Citron, K.M. and Standen S.M.: Effect of meals on rifampicin absorption.Lancet,2, 197 (1974).
Acocella, G.: Clinical pharmacokinetics of rifampicin.Clin. Pharmacokin.,3, 108 (1978).
Shim, C.K.: Clinical pharmacokinetics for dosage regiment establishment XVIII.Drug Information (Korean).7, 160 (1985).
Gibaldi, M., Perrier, D.:Pharmacokinetics, 2nd edition, Marcel Dekker Inc. New York (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Shim, CK., Lee, JU. Comparative study of rifampicin pharmacokinetics administered orally and intravenously in the fasted and non-fasted rats. Arch. Pharm. Res. 8, 177–186 (1985). https://doi.org/10.1007/BF02857043
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02857043