The pharmacokinetics of ziprasidone in healthy volunteers treated with cimetidine or antacid

Abstract

Aims: To evaluate the effects of cimetidine and Maalox(R) (aluminium hydroxide 1.35 g and magnesium hydroxide 1.2 g) on the pharmacokinetics of ziprasidone.

Methods: Eleven healthy young subjects aged 18-45 years were given single oral doses of ziprasidone 40 mg on three occasions at least 7 days apart. On one occasion ziprasidone was administered alone, on another occasion ziprasidone was co-administered with oral cimetidine 800 mg and on a third occasion ziprasidone was co-administered with oral Maalox(R).

Results: The administration of cimetidine increased the ziprasidone AUC(0,infinity) by 6% but there were no statistically significant differences in Cmax, tmax or lambda(z) between the ziprasidone+cimetidine group and the ziprasidone group. The administration of Maalox did not produce any statistically significant differences in AUC(0,infinity), Cmax, tmax or lambda(z) between the ziprasidone+Maalox group and the ziprasidone group.

Conclusions: The pharmacokinetics of ziprasidone are not affected by concurrent administration of cimetidine or Maalox. This suggests that other nonspecific inhibitors of cytochrome P450 and antacids are unlikely to alter the pharmacokinetics of ziprasidone.

Figure 1

Mean serum ziprasidone concentrations by treatment group (ziprasidone ◊; ziprasidone + Maalox®▪; ziprasidone + cimetidine ▴).

Figure 2

Individual AUC(0,∞) values by treatment group (ziprasidone ◊; ziprasidone + Maalox®▪; ziprasidone + cimetidine ▴). Group means are shown as horizontal dashed lines.

Figure 3

Individual C_max values by treatment group (ziprasidone ◊; ziprasidone + Maalox®▪; ziprasidone + cimetidine ▴). Group means are shown as horizontal dashed lines.