Enhancement of Oral Absorption of Metronidazole Suspension in Humans

Eur J Pharm Biopharm. 2000 Sep;50(2):213-6. doi: 10.1016/s0939-6411(00)00098-9.

Abstract

The purpose of this study was to investigate oral absorption of two metronidazole suspension products, Flagyl((R)) and a test product. Twenty-four healthy volunteers participated in the study. The crossover study was done in a two-phase, two-sequence manner with a 2-week washout period. Individual disposition kinetics were determined by non-compartmental analysis. AUC(0-infinity) and C(max) values were 1.26 and 1.86 times more in the case of test formulation. Mean plasma drug concentrations were analyzed to estimate the rate and extent of oral absorption. The optimized duodenal, jejunal1, jejunal2, illial1, ileal2, ilial3, ilial4, colonic permeability values (x10(-4)) for the test and Flagyl products were 3.96, 3.96, 3. 96, 0.68, 0.37, 0.01, 0.12, 0.38 and 2.34, 0, 0, 1.2, 1.1, 0.9, 0.3, 0.04cm/s, respectively. The total fraction of oral dose absorbed for the test and Flagyl products were 95.5% and 65.6% respectively, consistent with the pharmacokinetic ratios. The test product exhibited significantly higher absorption rate and extent than Flagyl, but both show similar half-lives. Sensitivity analysis showed that drug absorption is sensitive to effective permeability but not sensitive to particle radius and small intestinal transit time. The two products were found bio-inequivalent which is suggested to be due to differences in formulation additives that decreased the effective permeability of Flagyl.

MeSH terms

  • Absorption
  • Administration, Oral
  • Anti-Infective Agents / pharmacokinetics*
  • Area Under Curve
  • Humans
  • Male
  • Metronidazole / pharmacokinetics*
  • Suspensions

Substances

  • Anti-Infective Agents
  • Suspensions
  • Metronidazole