title: Assessing dopaminergic function in Parkinson's disease: levodopa kinetic-dynamic modeling and SPECT.
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.
authors.affiliation: Neurology Clinic, Department of Neurological Sciences, University of Bologna, Italy. contin@neuro.unibo.it
authors.forename: Manuela
authors.initials: M
authors.lastname: Contin
authors.forename: Paolo
authors.initials: P
authors.lastname: Martinelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Riva
authors.forename: Maurizio
authors.initials: M
authors.lastname: Dondi
authors.forename: Stefano
authors.initials: S
authors.lastname: Fanti
authors.forename: Cinzia
authors.initials: C
authors.lastname: Pettinato
authors.forename: Cesa
authors.initials: C
authors.lastname: Scaglione
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Albani
authors.forename: Agostino
authors.initials: A
authors.lastname: Baruzzi
mesh_terms: D000978:Antiparkinson Agents / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D003198:Computer Simulation; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006207:Half-Life; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000978:Antiparkinson Agents; D005462:Fluorine Radioisotopes; D007980:Levodopa; D004298:Dopamine