TY - JOUR
T1 - Assessing dopaminergic function in Parkinson's disease
T2 - Levodopa kinetic-dynamic modeling and SPECT
AU - Contin, Manuela
AU - Martinelli, Paolo
AU - Riva, Roberte
AU - Dondi, Maurizio
AU - Fanti, Stefano
AU - Pettinato, Cinzia
AU - Scaglione, Cesa
AU - Albani, Fiorenzo
AU - Baruzzi, Agostino
PY - 2003/12
Y1 - 2003/12
N2 - Levodopa pharmacokinetic-phamacodynamic (PK-PD) modeling may be able to test the functional integrity of the nigrostriatal dopaminergic system in Parkinson's disease (PD). [123I]-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 (t1/2eq) for PK-PD modeling and the ratio of specific to non specific (SP/NSP) tracer striatal uptake for SPECT. Levodopa t1/2eq 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.
AB - Levodopa pharmacokinetic-phamacodynamic (PK-PD) modeling may be able to test the functional integrity of the nigrostriatal dopaminergic system in Parkinson's disease (PD). [123I]-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 (t1/2eq) for PK-PD modeling and the ratio of specific to non specific (SP/NSP) tracer striatal uptake for SPECT. Levodopa t1/2eq 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.
KW - [I]-FP-CIT SPECT
KW - Levodopa
KW - Parkinson's disease
KW - Pharmacokinetic-pharmacodynamic modeling
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UR - http://www.scopus.com/inward/citedby.url?scp=1642553301&partnerID=8YFLogxK
U2 - 10.1007/s00415-003-0257-3
DO - 10.1007/s00415-003-0257-3
M3 - Article
C2 - 14673582
AN - SCOPUS:1642553301
VL - 250
SP - 1475
EP - 1481
JO - Journal of Neurology
JF - Journal of Neurology
SN - 0340-5354
IS - 12
ER -