Clinical Pharmacology 4

Special Populations

The age and the Effects of Sex - In the numerous dose (8 days of treatment) the study implicating 32 subjects, there was no difference in the pharmacokinetics of ziprasidone between the men and the women or between the rather old (> 65 years old) and young person (18 - 45 years) subjects. Supplémentairement, the pharmacokinetic population the valuation of patients in controlled trials revealed no obviousness of clinically significant age or of difference linked by sex in the pharmacokinetics of ziprasidone. The modifications of proportion for age or sex are not recommended, therefore.

Intramuscular Ziprasidone was not systematically assessed in the rather old patients (65 years and over).

Running - No study of specific pharmacokinetic was driven to investigate the effects of running. The pharmacokinetic population valuation revealed no obviousness of difference linked by running clinically significant in the pharmacokinetics of ziprasidone. The modifications of proportion for running are not recommended, therefore.

By smoking - Founded on in studies of vitro using human enzymes of liver, ziprasidone a substrate for CYP1A2 is not; tobacco addiction should therefore have no effect on the pharmacokinetics of ziprasidone. In harmony with these in results of vitro, the population pharmacokinetic valuation did not reveal difference pharmacokinetic significant between the smokers and the nonsmokers.

The Renal Weakening - since ziprasidone is highly transformed by metabolism, with less than 1 % medicaments excreted the only unchanged, renal weakening will not have probably impact mattering on the pharmacokinetics of ziprasidone. The pharmacokinetics of ziprasidone further to 8 days of proportion of OFFER of 20 mgs was similar among subjects with the variable levels of renal weakening (n=27) and subjects with normal renal function, by pointing out that the adaptation of proportion based on the level of renal weakening is not demanded. Ziprasidone is not taken away by hemodialysis.

The Hepatic Weakening - As ziprasidone are considerably cleared by the liver, they would expect that in the presence of hepatic weakening augments AUC of ziprasidone; a study of the numerous dose in the OFFER of 20 mgs for 5 days in subjects (n=13) with clinically significant (the Class A Childs-Pugh and B) the cirrhosis revealed an increase in AUC 0-12 of 13 % and of 34 % in the Class A Childs-Pugh and B, respectively, compared with a group of corresponded control (N=14). A half-life of 7.1 hours was noticed in subjects with the cirrhosis compared at 4.8 am in the group of control.

Intramuscular Ziprasidone was not systematically assessed in the rather old patients or in the patients with the hepatic or renal weakening. As the cyclodextrin excipient is clear by renal filtering, ziprasidone intramuscular should be managed with caution to the patients with weak renal function.

Reciprocal actions of medicament of the Medicament
One in the study of inhibition of enzyme vitro using the human liver microsomes showed that ziprasidone had not enough inhibitive effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 and would not interfere probably so the metabolism of medicaments principally transformed by metabolism by these enzymes. In vivo studies revealed no effect of ziprasidone on the pharmacokinetics of dextromethorphan, oestrogen, progesterone, or lithium.

In vivo studies revealed that a reduction about 35 % in ziprasidone AUC by concomitantly managed carbamazepine, an increase about 35-40 % in ziprasidone AUC by concomitantly managed ketoconazole, but any effect on the pharmacokinetics of ziprasidone by cimetidine or antiacid.