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  • Title: Assessing dopaminergic function in Parkinson's disease: levodopa kinetic-dynamic modeling and SPECT.
    Author: Contin M, Martinelli P, Riva R, Dondi M, Fanti S, Pettinato C, Scaglione C, Albani F, Baruzzi A.
    Journal: J Neurol; 2003 Dec; 250(12):1475-81. PubMed ID: 14673582.
    Abstract:
    Levodopa pharmacokinetic-phamacodynamic (PK-PD) modeling may be able to test the functional integrity of the nigrostriatal dopaminergic system in Parkinson's disease (PD). [(123)I]-FP-CIT SPECT imaging of striatal dopamine transporters has also been introduced for the evaluation of presynaptic dopaminergic homeostasis. We aimed to assess the intrapatient relation between levodopa PK-PD and SPECT measures of dopaminergic function in PD. Thirty-five PD patients, 1 to 4 on the Hoehn and Yahr (H&Y) scale, enrolled in the study. Each patient was examined by levodopa PK-PD modeling and SPECT imaging. Primary measure outcomes were the levodopa half-life in the effect compartment (t1/2(eq)) for PKPD modeling and the ratio of specific to non specific (SP/NSP) tracer striatal uptake for SPECT. Levodopa t1/2(eq) was highly significantly correlated with H&Y scale (r = -0.815, p < 0.0001), Unified Parkinson's disease Rating Scale (UPDRS) (r = -0.691, p < 0.0001) and PD symptom duration (r = -0.647, p < 0.0001). SPECT contralateral putamen SP/NSP ratio showed the most significant correlations with clinical indicators of disease severity: H&Y, r = -0.526, p < 0.002; UPDRS, r = -0.523, p < 0.002; symptom duration, r = -0.513, p < 0.002. Significant correlations were observed between levodopa t1/2(eq) and putamen SP/NSP ratios, yielding the closest correlation for the contralateral region (r = 0.522, p < 0.002). An indirect PK-PD dopaminergic functional variable and direct SPECT measures of presynaptic dopaminergic system homeostasis were in close agreement with clinical data and correlated to each other. Levodopa PK-PD modeling can be a practical clinical tool indirectly assessing the functional integrity of the nigrostriatal dopaminergic system in PD patients.
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