Tesis doctoral de María Penengo Salisbury
Abstract background: despite extensive literature on antipsychotic (ap) – induced d2 receptor occupancy (d2ro), it is still unclear which is the d2ro associated to symptom control in chronically dosed, stabilized schizophrenic patients as measured by 123i-ibzm single photon emission computed tomography (spect) and its relationship with ap pharmacokinetics (pk). Usually, d2ro is measured at a single time point after medication intake, and the influence of the scanning time within the ap interdose interval (i.I.) May be relevant for an adequate interpretation of d2ro measurements. aims: 1) to define the striatal d2ro in stabilized schizophrenic patients on clinically relevant doses of risperidone, olanzapine, clozapine and quetiapine using 123i-ibzm spect, and to investigate the relationship between d2ro and plasma concentration (cp) for these ap by means of an adequate cp . D2ro model. 2) to investigate the time course of ap – induced d2ro (d2ro-time model) and corresponding cp within the i.I. For each ap. 3) to investigate, by means of simulations, the influence of changes in specific parameters included in the abovementioned models on relevant model readouts. methods: forty-six schizophrenic patients (32m, 29.5+-6.5 yrs., Panss score 44.4+-8.4) stabilized on their clinically required doses of risperidone (n=12, 1.5-7 mg/day), olanzapine (n=12, 5-30 mg/day), clozapine (n=12, 50-600 mg/day) or quetiapine (n=10, 200-900 mg/day) were included. A 123i-ibzm spect scan was performed on each patient at a single time point after last dose intake. Patients within each ap group were randomly distributed in 4 subgroups of n=2-3, which were assigned a different scanning time based on known ap pk (the time of maximum plasma concentration tmax and the plasma half-life t1/2), as: pre-tmax, tmax, early after-tmax (before t1/2) and late after-tmax (after t1/2). For d2ro calculations, 123i-ibzm spect with mri co-registration and the tissue ratio method were
Datos académicos de la tesis doctoral «123i-ibzm assessed d2 receptor occupancy of atypical antipsychotics at clinically relevant doses in stabilized schizophrenic patients.«
- Título de la tesis: 123i-ibzm assessed d2 receptor occupancy of atypical antipsychotics at clinically relevant doses in stabilized schizophrenic patients.
- Autor: María Penengo Salisbury
- Universidad: Autónoma de barcelona
- Fecha de lectura de la tesis: 21/11/2006
Dirección y tribunal
- Director de la tesis
- Ana Catafau Alcantara
- Tribunal
- Presidente del tribunal: albert Badia sancho
- doménec Ros puig (vocal)
- Francisco Juan Lomeña caballero (vocal)
- victor Perez sola (vocal)