Good evening Dauntless,
Having recently reviewed the 1975 Imhof and 1981 Sioufi studies, I congratulate you on a thoughtful and eloquent assessment of the information--post # 2048--(and thank you for saving me some time tonight).
By the way, for those of you who don't have access to a medical library or who are short of time, the New York Public Library has a corporate services division that may be able to obtain the articles you want. They charge $30 - $50 per article, an hourly rate if research needs to be done, and a fax/delivery charge. And no, I do not have a financial interest in the NY Public Library.
As for Dauntless's post, no need to reiterate all he has written, but I'd like to emphasize a few points. I encourage you to understand post #2048 as I think it sheds light on the confusion surrounding the pharmacokinetics of standard release oral phentolamine vs. vasomax. Namely, the Imhof paper from 1975 does find that oral, commercially available (at the time) phentolamine given in doses of 20 to 40 mg did achieve maximum "unchanged drug" concentrations at 30 minutes. It states that they used both radioactively labelled carbon, and gas chromatography to obtain their results. The problem with this non-peer reviewed study is that there is no methodology, no controls, and does not explain how they differentiated free (unchanged drug) from conjugated (metabolized) drug. To my knowledge this study was never reproduced and in fact in 1978 was NOT used by Imhof to estimate plasma concentrations of phentolamine (instead using the less accurate method of measuring phentolamine plasma levels by measuring its effects on platelet aggregation). To me this study seems to be of questionable utility.
On the other hand, the Sioufi study includes a meticulous description of techniques used for gas chromatography (they were familiar with gas chromatography and had been using it in their lab for eight years prior to the writing of their article in 1981). In the Sioufi study they note that "very low plasma levels (of phentolamine) were measured at all sampling times (= 0.25 hr, 0.50 hr, 0.75 hr, 1.0 hr, and 2.0 hr). Unfortunately no actual ng data is given for plasma phentolamine via time (this study was focused on methodology) . However, urine levels of free and total phentolamine are graphed and show the greatest rate of urinary excretion of drug occurred between the second and third hours post oral administration.
The punch line is that in the International patent application to which I referred in post #1987, Zona repeated these studies SPECIFICALLY looking for plasma levels over time for standard release oral phentolamine, used gas chromatography (and included their methodology in detail), and found negligable (< 5.0 ng) levels of phentolamine up through 1.5 hours post oral administration. This is completely consistent with the Sioufi, but not the Imhof, study.
If I understand correctly then, the shorts believe part, if not all, of the following:
1) Zona is a "fraud and a scam"
2) Schering Plough (who had full access to all the study data and prior studies noted above) was hoodwinked and will be unable to market this product effectively
3) The Imhof article is substantive
4) Asencio (who by the way failed to include the standard release vs. vasomax plasma conentration over time data in his January 13,15 newswires regarding the second Zona patent application) is fair in his reporting
p.s. still waiting for an intelligent response to any of the questions raised in post # 1988 |
