Limits...
Comparison of D₂ dopamine receptor occupancy after oral administration of quetiapine fumarate immediate-release and extended-release formulations in healthy subjects.

Nord M, Nyberg S, Brogren J, Jucaite A, Halldin C, Farde L - Int. J. Neuropsychopharmacol. (2011)

Bottom Line: Peak D₂ receptor occupancy was significantly higher with quetiapine IR than XR in all subjects (50 ± 4% and 32 ± 11%, respectively), consistent with lower peak plasma concentrations for the XR formulation.The lower peak receptor occupancy associated with quetiapine XR may explain observed pharmacodynamic differences between the formulations.Assuming that our findings in control subjects are valid for patients with schizophrenia, the study supports the view that quetiapine, like the prototype atypical antipsychotic clozapine, may show antipsychotic effect at lower D₂ receptor occupancy than typical antipsychotics.

View Article: PubMed Central - PubMed

Affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska University Hospital, Stockholm, Sweden. Magdalena.Nord@ki.se

ABSTRACT
Quetiapine is an established drug for treatment of schizophrenia, bipolar disorder, and major depressive disorder. While initially manufactured as an immediate-release (IR) formulation, an extended-release (XR) formulation has recently been introduced. Pharmacokinetic studies show that quetiapine XR provides a lower peak and more stable plasma concentration than the IR formulation. This study investigated if the pharmacokinetic differences translate into different time curves for central D₂ dopamine receptor occupancy. Eleven control subjects were examined with positron emission tomography (PET) and the radioligand [11C]raclopride. Eight subjects underwent all of the scheduled PET measurements. After baseline examination, quetiapine XR was administered once-daily for 8 d titrated to 300 mg/d on days 5-8, followed by 300 mg/d quetiapine IR on days 9-12. PET measurements were repeated after the last doses of quetiapine XR and IR at predicted times of peak and trough plasma concentrations. Striatal D₂ receptor occupancy was calculated using the simplified reference tissue model. Peak D₂ receptor occupancy was significantly higher with quetiapine IR than XR in all subjects (50 ± 4% and 32 ± 11%, respectively), consistent with lower peak plasma concentrations for the XR formulation. Trough D₂ receptor occupancy was similarly low for both formulations (IR 7 ± 7%, XR 8 ± 6%). The lower peak receptor occupancy associated with quetiapine XR may explain observed pharmacodynamic differences between the formulations. Assuming that our findings in control subjects are valid for patients with schizophrenia, the study supports the view that quetiapine, like the prototype atypical antipsychotic clozapine, may show antipsychotic effect at lower D₂ receptor occupancy than typical antipsychotics.

Show MeSH

Related in: MedlinePlus

Arithmetic mean plasma concentration of quetiapine and norquetiapine during quetiapine IR (left) and XR (right) administration.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3198174&req=5

fig001: Arithmetic mean plasma concentration of quetiapine and norquetiapine during quetiapine IR (left) and XR (right) administration.

Mentions: The plasma concentrations of quetiapine were maximal at about 1.7 h after treatment with the IR formulation and about 5 h after administration of the XR formulation (Table 1, Fig. 1). Cmax for quetiapine (mean±s.d.) was 1850±820 nmol/l and 894±380 nmol/l for the IR and XR formulations, respectively. The difference between formulations was statistically significant (d.f.=11.0, t=3.18, p<0.01). At Tmax, the concentration of norquetiapine was 624±100 nmol/l for IR and 346±110 nmol/l for XR (d.f.=17.0, t=5.55, p<0.0001).


Comparison of D₂ dopamine receptor occupancy after oral administration of quetiapine fumarate immediate-release and extended-release formulations in healthy subjects.

Nord M, Nyberg S, Brogren J, Jucaite A, Halldin C, Farde L - Int. J. Neuropsychopharmacol. (2011)

Arithmetic mean plasma concentration of quetiapine and norquetiapine during quetiapine IR (left) and XR (right) administration.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198174&req=5

fig001: Arithmetic mean plasma concentration of quetiapine and norquetiapine during quetiapine IR (left) and XR (right) administration.
Mentions: The plasma concentrations of quetiapine were maximal at about 1.7 h after treatment with the IR formulation and about 5 h after administration of the XR formulation (Table 1, Fig. 1). Cmax for quetiapine (mean±s.d.) was 1850±820 nmol/l and 894±380 nmol/l for the IR and XR formulations, respectively. The difference between formulations was statistically significant (d.f.=11.0, t=3.18, p<0.01). At Tmax, the concentration of norquetiapine was 624±100 nmol/l for IR and 346±110 nmol/l for XR (d.f.=17.0, t=5.55, p<0.0001).

Bottom Line: Peak D₂ receptor occupancy was significantly higher with quetiapine IR than XR in all subjects (50 ± 4% and 32 ± 11%, respectively), consistent with lower peak plasma concentrations for the XR formulation.The lower peak receptor occupancy associated with quetiapine XR may explain observed pharmacodynamic differences between the formulations.Assuming that our findings in control subjects are valid for patients with schizophrenia, the study supports the view that quetiapine, like the prototype atypical antipsychotic clozapine, may show antipsychotic effect at lower D₂ receptor occupancy than typical antipsychotics.

View Article: PubMed Central - PubMed

Affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska University Hospital, Stockholm, Sweden. Magdalena.Nord@ki.se

ABSTRACT
Quetiapine is an established drug for treatment of schizophrenia, bipolar disorder, and major depressive disorder. While initially manufactured as an immediate-release (IR) formulation, an extended-release (XR) formulation has recently been introduced. Pharmacokinetic studies show that quetiapine XR provides a lower peak and more stable plasma concentration than the IR formulation. This study investigated if the pharmacokinetic differences translate into different time curves for central D₂ dopamine receptor occupancy. Eleven control subjects were examined with positron emission tomography (PET) and the radioligand [11C]raclopride. Eight subjects underwent all of the scheduled PET measurements. After baseline examination, quetiapine XR was administered once-daily for 8 d titrated to 300 mg/d on days 5-8, followed by 300 mg/d quetiapine IR on days 9-12. PET measurements were repeated after the last doses of quetiapine XR and IR at predicted times of peak and trough plasma concentrations. Striatal D₂ receptor occupancy was calculated using the simplified reference tissue model. Peak D₂ receptor occupancy was significantly higher with quetiapine IR than XR in all subjects (50 ± 4% and 32 ± 11%, respectively), consistent with lower peak plasma concentrations for the XR formulation. Trough D₂ receptor occupancy was similarly low for both formulations (IR 7 ± 7%, XR 8 ± 6%). The lower peak receptor occupancy associated with quetiapine XR may explain observed pharmacodynamic differences between the formulations. Assuming that our findings in control subjects are valid for patients with schizophrenia, the study supports the view that quetiapine, like the prototype atypical antipsychotic clozapine, may show antipsychotic effect at lower D₂ receptor occupancy than typical antipsychotics.

Show MeSH
Related in: MedlinePlus