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Pharmacokinetics and Therapeutics of Acute Intramuscular Ziprasidone

Clinical Pharmacokinetics volume 44, pages 1117–1133 (2005)Cite this article

Abstract

Patients with acute psychosis often exhibit agitation, which can be distressing and hazardous to others as well as to the patient. In such psychiatric emergencies, intramuscular antipsychotic agents can be easier to administer than oral formulations, and they have the added advantage of more rapid absorption and a faster onset of action. However, intramuscular formulations of conventional antipsychotics, which have been the standard treatment, are associated with acute dystonia and other movement disorder-related adverse events. Ziprasidone is the first atypical antipsychotic to be clinically available in both intramuscular and oral formulations in the US. The intramuscular formulation of ziprasidone, ziprasidone mesylate, uses sulfobutylether β-cyclodextrin to solubilise the drug by complexation. The pharmacokinetics of intramuscular ziprasidone include rapid attainment of therapeutic drug level (time to reach peak serum concentration [tmax] ≤60 minutes postdose), a mean terminal elimination half-life ranging from 2 to 5 hours, bioavailability of approximately 100%, exposure to drug that increases in a dose-related manner and little drug accumulation even after 3 days of repeated intramuscular administration.

The metabolism and elimination of intramuscular ziprasidone have not been extensively evaluated. The principal difference between any oral versus intramuscular formulations of a drug is in first-pass metabolism. Oral ziprasidone is eliminated mainly via the hepatic route and <1 % is eliminated in urine and <4% in faeces as unchanged drug. That would not be expected to change with the intramuscular route of administration. Low concentrations of ziprasidone are seen 12–18 hours after the last intramuscular injection. The rapid clearance of ziprasidone from plasma after an intramuscular administration results in little to no persistence of plasma drug level when switching from intramuscular to oral drug administration. No clinically significant age-, sex- or race-related effects on the pharmacokinetics of intramuscular or oral ziprasidone have been noted, and the tolerability and cardiovascular safety profiles of intramuscular ziprasidone have been well characterised in clinical trials.

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Acknowledgements

A fellow of the American Psychiatric Association and the American Psychopathological Association, Sheldon H. Preskorn, MD, has served on advisory and review committees for the US FDA, the Veterans Administration, the National Institutes of Health and the National Science Foundation, and was a psychopharmacology consultant to the Menninger Foundation.

Dr Preskorn personally owns no stock in any pharmaceutical company other than what might have been purchased in externally managed accounts.

His activities with the pharmaceutical industry have included serving as a consultant and researcher at all phases of drug development (preclinical through to registration) and as a sponsored speaker at a wide variety of educational programmes. He has served, or is serving in one or more of the following capacities: as a principal investigator, on the Speakers’ Bureau, and/or as a consultant for the following companies: Abbott Laboratories, AstraZeneca, Aventis, Bayer, Biovail, Boehringer-Ingelheim, Bristol-Myers Squibb, E. Merck, Eisai, Eli Lilly, GlaxoSmithKline, Forest, Hoffman-LaRoche, Innapharma, Janssen, Johnson & Johnson, Lundbeck, Merck, Neurosearch, Novartis, Organon, Otsuka, Pfizer Inc., Sention, Solvay, Sommerset, Sumitomo, Wyeth, and Yamanouchi.

Dr Preskorn was the principal investigator on a number of phase I studies with both intravenous and intramuscular formulations of ziprasidone, as well as phase II and III efficacy trials of the intramuscular formulation.

Research assistance, editorial assistance and an honorarium for the preparation of this article was provided by Pfizer Inc.

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  1. Department of Psychiatry, University of Kansas School of Medicine-Wichita and the Clinical Research Institute, Wichita, Kansas, USA

    Sheldon H. Preskorn

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Preskorn, S.H. Pharmacokinetics and Therapeutics of Acute Intramuscular Ziprasidone. Clin Pharmacokinet 44, 1117–1133 (2005). https://doi.org/10.2165/00003088-200544110-00002

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Keywords

  • Haloperidol
  • Ziprasidone
  • Brief Psychiatric Rate Scale
  • Peak Serum Concentration
  • Aldehyde Oxidase