Comparative analysis of the effects of rice and bread meals on bioavailability of itraconazole using NONMEM in healthy volunteers

Eur J Clin Pharmacol. 2006 Dec;62(12):1033-9. doi: 10.1007/s00228-006-0200-5. Epub 2006 Oct 20.

Abstract

Objective: The objectives of this retrospective study were to examine the relationship between the bioavailability of itraconazole and the type of food consumed and to determine the effects of food consumption on the pharmacokinetic parameters following a single oral dose of itraconazole in healthy volunteers.

Methods: The plasma itraconazole concentration-time data were pooled from four pharmacokinetic studies in 144 healthy subjects. Individual pharmacokinetic values were estimated as model-independent (AUC, C (max), and T (max)) and model-dependent (T (lag), K (a), K (cp), K (pc), K (el), and V (d)/F; two-compartment open model with lag time) parameters using the WinNonlin software program. We estimated the population characteristics of the food effects using NONMEM.

Results: The consumption of a bread meal before the administration of itraconazole caused a significant increase in its bioavailability, as well as increases in the peak plasma concentration and lag time for itraconazole absorption. On the contrary, consumption of a rice meal before the administration of itraconazole caused a significant decrease in its bioavailability.

Conclusion: Therefore, although a dose of itraconazole is normally administered immediately after a meal to increase its bioavailability, this is not an effective strategy after a rice meal.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Algorithms
  • Analysis of Variance
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / blood
  • Antifungal Agents / pharmacokinetics
  • Area Under Curve
  • Biological Availability
  • Bread*
  • Capsules
  • Chromatography, High Pressure Liquid / methods
  • Cluster Analysis
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Eating / physiology*
  • Female
  • Food-Drug Interactions
  • Humans
  • Itraconazole / administration & dosage
  • Itraconazole / blood
  • Itraconazole / pharmacokinetics*
  • Male
  • Oryza*
  • Retrospective Studies
  • Software*
  • Time Factors

Substances

  • Antifungal Agents
  • Capsules
  • Itraconazole