[QUOTE=johnt;1228202]Therapies that give PwPs better control of levodopa levels (and, hence, dopamine) are to be welcomed. But I do have a number of concerns about the levodopa inhaler's practical use.

A PwP suffering regular "off" periods is likely to be under-medicated. The fact that this state of affairs has been allowed to occur indicates poor medical management of the disease. For instance, a typical 6 monthly schedule of visits to the neurologist is too infrequent for some PwP to be able to titrate doses upward fast enough as required by the progression of the disease. The inhaler may help, but it would seem better to solve the problem by conventional means, by increasing the dose or increasing the frequency of the doses.

Irregular off periods may be caused by interactions with foods, especially proteins, and the timing of gastric emptying. The inhaler has more of a role to play here. But one problem is that, at least for me, sometimes the effect of a dose is delayed, but does come eventually. The danger is that a PwP may use the inhaler just before the original dose kicks in, which combined will result in very high levodopa levels.

I am also concerned that the more rapid response to a dose may increase addiction levels.

Talking generally, the pharmacokinetic/pharmacodynamic model which seems to fit my own symptoms is that I have a threshold of levodopa plasma levels, below which I am "off" and above which I am "on". Unfortunately, levodopa has a short half-life (about 90 minutes) so if the dose is just large enough to get you to the threshold, but not beyond, the decline back below the threshold would end the "on" just as soon as it started. To get longer "on" times using plain C/L requires taking a dose which results in levels well above those necessary to get to the threshold. For instance, taking a dose which takes you to plasma levels twice that required to get "on" gives you an "on" duration equal to the half life. This leads to varying levodopa levels, which is undesirable. Alternatively, you must increase the frequency of the doses or find some way of increasing reservoirs of dopamine.

See my web page:
Parkinson's Disease Measurement: PwP, surveys, trials, analysis
You input the drugs that you use each day and the program draws graphs of how plasma levels vary over time.

John[/QUO

bottom line, advanced pd'ers with optimized drug dosing need a better rescue option than injectable apomorphine, especially those that are only on C/L. There is also a sublingual apomorphine strip which i believe will soon be approved. It would be interesting to see how quickly one goes on taking this inhaled l-dopa after eating >20 grams of protein. it still has to compete with all those amino acids to get into the brain. wonder if apomorphine is absorbed differently. i guess checking if there is protein interference with duodopa gel would shed light on this.