Niggs, a good set of questions. We could answer those questions if we could answer the following question.

What is the mechanism by which constipation affects the bioavailability of levodopa?

I must admit that when I wrote the conjectures I was mainly thinking about my personal experience which, in this context, and put simply, is that my PD is worse when I am constipated.

These matters have been discussed before. See the thread, "Docs Ignore Constipation in Parkinson's", started by GerryW:

http://neurotalk.psychcentral.com/sh...t=constipation

My constipation is worse now than it was when I posted to that thread. It is now unusual for me to "go" in less than five days. (Or, rather, it was before I started taking enemas regularly. But, that will be the subject of another post.)

I can't find a scientific paper that explicitly reports that constipation reduces the bioavailability of levodopa. The closest I can get is:

"Since levodopa is absorbed from the small intestine ... bowel dysfunction in PD may interfere with levodopa absorption, worsen the motor disorder, or even lead to malignant syndrome ..." [1]

But, I suggest two mechanisms that may cause it:

1. Toxin build up due to constipation, as posted in the thread referenced above by Rick.

2. The presence of stool at the absorption sites.

Note: as I understand it, in terms of the normal flow of materials, food goes through the stomach, followed by the small intestines, followed by the large intestines.

Based on dog studies, Sasahara et al. [2] report that "the major absorption site of levodopa in the intestine resides in the upper small intestine", with the jejunum, ileum and duodenum all playing a part. The case then rests on whether under conditions of severe constipation stool gets into the small intestine.

Certainly, the large intestine can be blocked by a "hard mass of stool" [3]. But it can go further back.

"An obstruction can occur ... anywhere in the small or large intestine, and there can be a partial or complete blockage. ...
About 20% of hospital admissions for acute abdominal pain are due to a bowel obstruction and the majority of these occur in the small intestine." [4]

References

[1] Parkinson's Disease
Volume 2011 (2011), Article ID 924605, 21 pages
http://dx.doi.org/10.4061/2011/924605
"Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease"
Ryuji Sakakibara,1 Masahiko Kishi,1 Emina Ogawa,1 Fuyuki Tateno,1 Tomoyuki Uchiyama,2 Tatsuya Yamamoto,2 and Tomonori Yamanishi
http://www.hindawi.com/journals/pd/2011/924605/

[2] J Pharm Sci. 1981 Oct;70(10):1157-60.
"Dosage form design for improvement of bioavailability of levodopa V: Absorption and metabolism of levodopa in intestinal segments of dogs."
Sasahara K, Nitanai T, Habara T, Morioka T, Nakajima E.
http://www.ncbi.nlm.nih.gov/pubmed/7299652

[3] http://www.webmd.com/digestive-disor...topic-overview

[4] http://www.webmd.boots.com/digestive...el-obstruction

John