Pharmacokinetics Of Ziprasidone Research Articles

Physiologically-based pharmacokinetics of ziprasidone in pregnant women.

Pregnancy is associated with physiological changes that alter the pharmacokinetics (PK) of drugs. The aim of this study was to predict the PK of ziprasidone in pregnant women. A full physiologically-based pharmacokinetic (PBPK) model of ziprasidone was developed and validated for the non-pregnant population (healthy adults, paediatrics, geriatrics), and this was extended to the pregnant state to assess the change in PK profile of ziprasidone throughout pregnancy. The PBPK model successfully predicted the ziprasidone disposition in healthy adult volunteers, wherein the predicted and observed AUC, Cmax and tmax were within the fold-difference of 0.94-1.09, 0.89-1.40 and 0.80-1.08, respectively. The paediatric and geriatric population, also showed predicted AUC, Cmax and tmax within a two-fold range of the observed values. The simulated exposure in pregnant women using a p-PBPK model showed no significant difference when compared to non-pregnant women. The PBPK model predicted the impact of physiological changes during pregnancy on PK and exposure of ziprasidone, suggesting that dose adjustment is not necessary in this special population.

Therapeutic Drug Monitoring of Ziprasidone in a Clinical Treatment Setting

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.

Pharmacokinetics of ziprasidone in children and adolescents with Tourette's syndrome

Pharmacokinetics of ziprasidone in children and adolescents with Tourette's syndrome

Introduction

Introduction

P.2.068 The pharmacokinetics of ziprasidone in subjects with normal and impaired renal function

P.2.068 The pharmacokinetics of ziprasidone in subjects with normal and impaired renal function

P.2.090 The pharmacokinetics of ziprasidone in subjects with normal and impaired hepatic function

A series of new 10-methoxypyrazino[1,2-a]indoles has been prepared and shown to be 5HT2C receptor ligands. The studied compounds 10a–j were found to act as partial agonists at the 5HT2C receptor, binding with high affinity and moderate selectivity versus 5HT1A and 5HT2A receptors, but inducing only a submaximal increase in phosphoinositol formation. Compound 10j was demonstrated to be active in animal models of obsessive-compulsive disorder, depression and panic anxiety.