title: Therapeutic drug monitoring of ziprasidone in a clinical treatment setting.
abstract: There is limited information on the pharmacokinetics ofziprasidone (ZIP) in naturalistic clinical settings. The objective of this study was to investigate the concentrations of ZIP and its active metabolite S-methyl-dihydroziprasidone (SMDZ), and the dose-normalized concentrations, using routine therapeutic drug monitoring (TDM) data. A high-performance liquid chromatographic method for determining serum concentrations of these substances for routine clinical use was established at the TDM Laboratory in Linköping, Sweden. This analytical service was available to all physicians in Sweden. Between January 2001 and December 2004, 545 analyses, representing samples from 370 patients, were performed. The median daily ZIP dose was 120 mg (range 20 -320 mg). In all, 121 steady-state trough specimens with essential clinical information were included in the pharmacokinetic evaluation. The median (25th to 75th percentile) serum concentration of ZIP was 125 nmol/L (82-188 nmol/L). The SMDZ:ZIP ratio decreased with increasing serum concentration of ZIP. The median (25th to 75th percentile) dose-normalized concentrations (nmol L(-1) mg(-1) d(-1) forZIPand SMDZ were 1.13 (0.74-1.77) and 0.62 (0.45-0.86), respectively,with SMDZ:ZIP ratio of 0.57 (0.42-0.79). The overall coefficients of variation for dose-normalized serum concentrations of ZIP, SMDZ, andSMDZ:ZIP ratio were 62%, 56%, and 57%, respectively (n = 121). Smoking women had lower normalized ZIP concentrations than nonsmoking women. Twenty-eight patients with repeated eligible TDM analyses were studied for intraindividual variance over time. In summary, great interindividual and intraindividual differences in ZIPconcentrations were observed. TDM of ZIP maybe used for individual dose adjustments and monitoring medication adherence.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Health Sciences, Linkoping University Hospital, Sweden. maria.dolores.cherma.yeste@lio.se
authors.forename: Maria D
authors.initials: MD
authors.lastname: Chermá
authors.forename: Margareta
authors.initials: M
authors.lastname: Reis
authors.forename: Staffan
authors.initials: S
authors.lastname: Hägg
authors.forename: Johan
authors.initials: J
authors.lastname: Ahlner
authors.forename: Finn
authors.initials: F
authors.lastname: Bengtsson
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D002648:Child; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D011358:Product Surveillance, Postmarketing; D012727:Sex Characteristics; D012907:Smoking; D013844:Thiazoles / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; C535018:S-methyl-dihydroziprasidone; D013844:Thiazoles; C092292:ziprasidone