Ziprasidone and Methyldihydroziprasidone Kinetics as Displayed in the Naturalistic Clinical Setting by Applying a TDM-Routine

Objective: The aims of the project were to develop 1) a TDM-routine for ziprasidone and a major metabolite as well as 2) to use consecutively collected TDM-material from the naturalistic clinical setting for a scientific-founded post-marketing surveillance report of the „true“ kinetics for the new drug when exposed to the naturalistic clinical setting.

Methods: Ziprasidone was approved for treatment of psychosis in Sweden in September 2000. A Therapeutic Drug Monitoring (TDM) service was developed for determination of trough level ziprasidone (ZIP) and methyl-dihydro-ziprasidone (MDZ) at steady-state. This service was offered by a so called „Site Management Organisation“ (Berzelius Clinical Research Center AB; BCRC) in collaborating with the Department of Clinical Pharmacology at Linköping University, making an agreement for this procedure financed via the responsible drug company. BCRC is a joint-stock company owned by the regional County Council. BCRC is specialised in performing clinical trials, one section being developed as „A bridge-of-knowledge concept to link pharmacology and psychiatry providing and evaluating TDM-services of novel psychoactive drugs. This drug analytical service and the linked clinical pharmacological interpretation as well as the evaluation process was made available to all TDM-requiring physicians in Sweden (catchments area of about 9 million inhabitants).

Results: From February 2001 to May 2004, 461 serum samples of ziprasidone and its main metabolite from 338 patients were requested and analysed. These samples were accompanied with clinical information in a specific TDM referral form. The samples represented patients ranging between 11–83 years of age, and of doses ranging between 20 and 280mg per day (recommended doses are 80–160mg per day). Stratified and worked-up data on the clinical as well as pharmacokinetic detailed results from these consecutively collected and analysed TDM-samples from the present investigation will be presented.