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Keywords:

  • antacid;
  • bioavailability;
  • drug absorption;
  • drug interaction;
  • itraconazole;
  • pharmacokinetics

Summary

Aims:  To investigate the effects of antacid suspension on oral absorption of itraconazole.

Methods:  A randomized, open-labelled, two-period, crossover study with a 1-week washout period was conducted in 12 healthy Thai male volunteers. The participants were allocated in either treatment A or B in the first period. In treatment A, the volunteers were orally administered with 200 mg of itraconazole alone. In treatment B, the volunteers were administered orally with 200 mg of itraconazole co-administered with antacid suspension. Serial serum samples were collected over the period of 24 h and subsequently analysed by using a validated high-pressure liquid chromatographic method with ultraviolet detection. Pharmacokinetic parameters were determined by non-compartmental analysis.

Results:  Time to reach maximal concentration (Tmax), maximal concentration (Cmax) and area under the curve (AUC0--∞) were markedly decreased in antacid-treated group. Tmax for treatment A was 3·0 ± 0·4 and 5·1 ± 2·7 h for treatment B. Cmax and AUC0--∞ of treatments A and B were 146·3 ± 70·5 vs. 43·6 ± 16·9 (ng/mL) and 1928·5 ± 1114·6 vs. 654·8 ± 452·2 (ng·h/mL) respectively. 90% Confidence interval (90% CI) of Cmax and AUC0--∞ were 24·1–42·1 and 16·2–65·9 respectively.

Conclusions:  Rate and extent of itraconazole oral absorption were markedly decreased by concurrent use of antacid suspension. Hence, co-administration of itraconazole and antacid suspension should be avoided.