Carbidopa is also claimed to be unable to cross the BBB, but it has been shown that it can cross a defective BBB, and PWP have defective BBB's!! A fact researchers tend to forget. Once in the brain, it would prevent decarboxylation of levodopa to dopamine. However, I can't give an explanation why this should happen at the end of an on, causing the catastrophic off some of us see.
The latest paper by Leenders on PWP's having defective BBB's is below.
Ron

J Neural Transm. 2008 Jul;115(7):1001-9. Epub 2008 Feb 12. Links
Decreased blood-brain barrier P-glycoprotein function in the progression of Parkinson's disease, PSP and MSA.Bartels AL, Willemsen AT, Kortekaas R, de Jong BM, de Vries R, de Klerk O, van Oostrom JC, Portman A, Leenders KL.
Department of Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. a.l.bartels@neuro.umcg.nl

Decreased blood-brain barrier (BBB) efflux function of the P-glycoprotein (P-gp) transport system could facilitate the accumulation of toxic compounds in the brain, increasing the risk of neurodegenerative pathology such as Parkinson's disease (PD). This study investigated in vivo BBB P-gp function in patients with parkinsonian neurodegenerative syndromes, using [11C]-verapamil PET in PD, PSP and MSA patients. Regional differences in distribution volume were studied using SPM with higher uptake interpreted as reduced P-gp function. Advanced PD patients and PSP patients had increased [11C]-verapamil uptake in frontal white matter regions compared to controls; while de novo PD patients showed lower uptake in midbrain and frontal regions. PSP and MSA patients had increased uptake in the basal ganglia. Decreased BBB P-gp function seems a late event in neurodegenerative disorders, and could enhance continuous neurodegeneration. Lower [11C]-verapamil uptake in midbrain and frontal regions of de novo PD patients could indicate a regional up-regulation of P-gp function.

PMID: 18265929 [PubMed - indexed for MEDLINE]
PMCID: PMC24