Single- and multiple-dose pharmacokinetics of ziprasidone in healthy youngand elderly volunteers

Aims To compare the pharmacokinetics of ziprasidone in healthy young (18-45 years) men and women, and healthy elderly (greater than or equal to 65 yea rs) men and women. Methods Eight young men, 11 young women, 8 elderly men and 8 elderly women were given oral ziprasidone 40 mg day(-1), in two evenly divided daily dose s, for 7 days, followed by a single 20 mg dose on day 8. Serum samples were collected immediately before the morning dose on days 1-8, for up to 12 h after dosing on day 1 and for up to 96 h after dosing on day 8. The resulti ng data were used to derive pharmacokinetic parameters of ziprasidone in ea ch age and gender group. Results Steady-state serum concentrations of ziprasidone were achieved with in 2-3 days. The steady-state pharmacokinetics of ziprasidone, determined 8 days after the initiation of treatment, were similar in the young men, eld erly men and young women. Assessment of gender effects by analysis of varia nce revealed statistically significant differences in C-max (85 vs 69 ng ml (-1)) and t(max), (3.19 vs 4.81 h) but no differences in AUC(0,12 h) or lam bda(z). Assessment of age effects by analysis of variance revealed statisti cally significant differences in AUC(0,12 h) (560 vs 465 ng ml(-1) h), C-ma x (85 vs 69 ng ml(-1)) and lambda(z) (0.126 vs 0.1971h(-1)) but no differen ce in t(max). Assessment of age and gender effects by analysis of covarianc e, with body weight as the covariate, did not reveal any significant differ ences. The mean t(1/2,z), in the young men, young women, elderly men and el derly women were 3.1, 4.1, 5.7 and 5.3 h, respectively. Standard deviations of the means for the pharmacokinetic parameters for the elderly women tend ed to be large. Conclusions The influence of age and gender on the pharmacokinetics of zipr asidone is not clinically significant.