Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Diagnostic radiopharmaceutical central nervous system, ATC code: V09AB03.
Due to the low quantities of ioflupane injected, pharmacological effects are not expected following intravenous administration of DaTSCAN at the recommended dosage.
Mechanism of action
Ioflupane is a cocaine analogue. Studies in animals have shown that ioflupane binds with high affinity to the presynaptic dopamine transporter and so radiolabelled ioflupane (123I) can be used as a surrogate marker to examine the integrity of the dopaminergic nigrostriatal neurons. Ioflupane also binds to the serotonin transporter on 5-HT neurons but with lower (approximately 10-fold) binding affinity.
There is no experience in types of tremor other than essential tremor.
Clinical efficacy
Clinical studies in patients with dementia with Lewy bodies
In a pivotal clinical trial including evaluation of 288 subjects with dementia with Lewy bodies (DLB) (144 subjects), Alzheimer's disease (124 subjects), vascular dementia (9 subjects) or other (11 subjects), the results of an independent, blinded visual assessment of the DaTSCAN images were compared to the clinical diagnosis as determined by physicians experienced in the management and diagnosis of dementias. Clinical categorisation into the respective dementia group was based on a standardised and comprehensive clinical and neuropsychiatric evaluation. The values for the sensitivity of DaTSCAN in determining probable DLB from non-DLB ranged from 75.0% to 80.2% and specificity from 88.6% to 91.4%. The positive predictive value ranged from 78.9% to 84.4% and the negative predictive value from 86.1% to 88.7%. Analyses in which both possible and probable DLB patients were compared with 


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non-DLB dementia patients demonstrated values for the sensitivity of DaTSCAN ranging from 75.0% to 80.2% and specificity from 81.3% to 83.9% when the possible DLB patients were included as non-DLB patients. The sensitivity ranged from 60.6% to 63.4% and specificity from 88.6% to 91.4% when the possible DLB patients were included as DLB patients.

Clinical studies demonstrating adjunctive use of semi-quantitative information for image interpretation The reliability of using semi-quantitative information as an adjunct to visual inspection was analysed in four clinical studies where sensitivity, specificity or overall accuracy between the two methods of image interpretation were compared. In the four studies (total n=578), CE-marked DaTSCAN semi-quantitation software was used. The differences (i.e., improvements when adding semi-quantitative information to visual inspection) in sensitivity ranged between 0.1% and 5.5%, in specificity between 0.0% and 2.0%, and in overall accuracy between 0.0% and 12.0%.
The biggest of these four studies retrospectively assessed a total of 304 DaTSCAN exams from previously conducted Phase 3 or 4 studies, which included subjects with a clinical diagnosis of PS, non- PS (mainly ET), probable DLB, and non-DLB (mainly AD). Five nuclear medicine physicians who had limited prior experience with DaTSCAN interpretation assessed the images in 2 readings (alone and combined with semi-quantitative data provided by DaTQUANT 4.0 software) at least 1 month apart.
These results were compared with the subject’s 1-to 3-year follow-up diagnosis to determine diagnostic accuracy. The improvements in sensitivity and specificity [with 95% confidence intervals] were 0.1% [- 6.2%,6.4%] and 2.0% [-3.0%,7.0%]. Also, the results of the combined reading were associated with an increase in reader confidence.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Distribution
Ioflupane (123I) is cleared rapidly from the blood after intravenous injection; only 5% of the administered activity remains in whole blood at 5 minutes post-injection.
Organ uptake
Uptake in the brain is rapid, reaching about 7% of injected activity at 10 minutes post-injection and decreasing to 3% after 5 hours. About 30% of the whole brain activity is attributed to striatal uptake.
Elimination
At 48 hours post-injection, approximately 60% of the injected radioactivity is excreted in the urine, with faecal excretion calculated at approximately 14%.