Ziprasidone pharmacokinetics

Miceli JJ, Smith M, Robarge L, Morse T, Laurent A. The effects of ketoconazole on ziprasidone pharmacokinetics—a placebo-controlled crossover study in healthy volunteers. Br J Clin Pharmacol 2000 49(Suppl. 1) 71S-6S. 

Sallee, F.R., Miceli, J.J., Wilner, K.D., and Robarge, L. (2000b) Pharmacokinetics of ziprasidone in children and adolescents with Tourette s syndrome. In New Research Abstracts from the American Psychiatric Association Annual Meeting, Chicago, IL NR563. 

Ziprasidone s pharmacokinetics permit rapid and predictable dose adjustment, with metabolites that are considered to be clinically inactive ( 134). The results of PET pharmacokinetic and pharmacodynamic studies indicate that a twice daily dosage regimen is appropriate. 

TABLE 5-27. Pharmacokinetics of risperidone, olanzapine, quetiapine, and ziprasidone... 

Antipsychotics produce more important pharmacodynamic than pharmacokinetic interactions because of their multiple effects. Additive effects may occur when these drugs are combined with others that have sedative effects, a-adrenoceptor-blocking action, anticholinergic effects, and—for thioridazine and ziprasidone—quinidine-like action. 

Muirhead GJ, Harness J, Holt PR, Oliver S, Anziano RJ. Ziprasidone and the pharmacokinetics of a combined oral contraceptive. Br J Clin Pharmacol 2000 49(Suppl l) S49-56. 

Pfizer, the marketing authorization holder of ziprasidone, has promoted several pharmacokinetic studies. Oral contraceptives (ethinylestradiol 30 pg/day plus levonorgestrel 150 pg/day) (34), lithium 900 mg/day (35), ketoconazole 400 mg/day (36), and carbamazepine (100-400 mg/day)... 

Ziprasidone is oxidatively metabolized by CYP3A4, but it does not inhibit CYP3A4 or other isoenzymes at clinically relevant concentrations. The effect of ketoconazole 400 mg qds for 6 days on the single-dose pharmacokinetics of ziprasidone 40 mg has been evaluated in an open, placebo-controlled, crossover study in healthy volunteers... 

Ketoconazole caused a modest increase in the mean AUC (33%) and the mean Cmax (34%) of ziprasidone. This effect was not considered clinically relevant and suggests that other inhibitors of CYP3A4 are unlikely to affect the pharmacokinetics of ziprasidone significantly. Most of the reported adverse events were mild. The adverse events that were most commonly reported in subjects who took the drugs concomitantly were dizziness, weakness, and somnolence. There were no treatment-related laboratory abnormalities or abnormal vital signs during the study and at the 6-day follow-up evaluation. 

Preskorn SH. Pharmacokinetics and therapeutics of acute intramuscular ziprasidone. Chn Pharmacokinet 2005 44 1117-33. 

The effect of steady-state carbamazepine administration on the steady-state pharmacokinetics of ziprasidone has been studied in 25 healthy young adults, in a randomized, placebo-controlled study (112). Carbamazepine caused small reductions in ziprasidone AUCo i2 and Cmax (36% and 27% respectively). The authors concluded that carbamazepine had increased ziprasidone clearance by induction of CYP3A4. 

A study with the potent CYP 3 A4 inhibitor ketoconazole showed minimal effects on ziprasidone single-dose pharmacokinetics, with only a 33% mean increase in the ziprasidone area under the time-versus-concentration curve. " These results are consistent with data suggesting that aldehyde oxidase is the major metabolic pathway for ziprasidone, with only 30% to 35% being metabolized by CYP 3A4. ... 

Low doses of carbamazepine do not appear to affect the pharmacokinetics of ziprasidone. 

Miceli JJ, Anziano RJ, Robarge L, Hansen RA. Laurent A. The effect of carbamazepine on the steady-state pharmacokinetics of ziprasidone in healdiy volunteers. Br J Clin Pharmacol (2000) 49 (Siq)pl 1), 65S-70S. 

Ziprasidone does not appear to aiter the pharmacokinetics of lithium. 

A single 40-mg oral dose of ziprasidone were given to 10 healthy subjects either alone, with cimetidine 800 mg daily for 2 days, or with three 30-mL doses of Maalox (aiuminium/magnesium hydroxide). The only change in the pharmacokinetics of ziprasidone was a 6% increase in the AUC with cimetidine. It was concluded that no special precautions are needed if ei-... 

The manufaeturers say that population pharmaeokinetie analysis of schizophrenic patients who were enrolled in elinieal studies showed that no significant pharmacokinetic interactions occurred with benzatropine, Iorazepam or propranolol. The manufacturers also point out that since ziprasidone is not metabolised by the cytochrome P450 isoenzyme CYP1A2, smoking should not affect its pharmacokinetics. This is borne out by studies in patients, which did not reveal any differences in the pharmacokinetics of ziprasidone between tobacco smokers and non-smokers. ... 

Wilner KD, Hansen RA, Folger CJ, Geoffioy P. The pharmacokinetics of ziprasidone in heald volunteers treated with cimetidine or antacid BrJ Clin PhamuKol (2000) 49 (Suppl 1), 57S-60S. 

In a placebo-controlled, crossover study, 18 women taking an oral contraceptive (ethinylestradiol/levonorgestrei 30/150 micrograms) for at least 3 months were also given ziprasidone 20 mg twice daily for 8 days. The only change in the pharmacokinetics of the two steroids was an approximately 30-minute increase in the time to maximum plasma concentration of the levonorgestrel, but this was not considered to be clinically significant. No adverse effects occurred. It was concluded that combined use is safe and that ziprasidone does not affect the efficacy of this oral contraceptive and is also unlikely to affect the metabolism and therefore effieaey of other similar contraceptives. 

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