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Author's reply

Carrupt and Testa's letter concerning my recent article in The British Journal of Radiology [1], again explains their technique as previously published [2].

Carrupt and Testa question the use of the term "experiment". An experiment is "a procedure meant to yield or illustrate a principle, effect, or fact" [3], a definition which applies the content of my article.

Their remarks concerning the use of the partition coefficient to compare monomers are perplexing. One of the participating authors of the article they defend [2] co-authored another paper linking hydrophilicity, partition coefficient values and "even" distribution hydrophilic substituents [4]. I used their values of the LogP in my article and due credit was given!

The major problem with the article [2] proposing the "hydrophilic protection sphere of iobitridol (Xenetix)" lies in the fact that a theory is proposed for and on the basis of the study of one single molecule. My paper (with the inherent limitations of the study type as was mentioned in the article) tried to investigate, in a basic way, if other similar molecules behaved in the same way as far as rotational barriers were concerned. The method of semi-empirical theory is questioned by Carrupt and Testa. The semi-empirical level of theory (as implemented in the Mopac/Ampac software) is well suited for this purpose, namely the computation of rotational barriers [5]. Let it by the way be mentioned that Meyer, Carrupt and Testa, in their own paper [2], also used Mopac to calculate rotational barriers! I did nothing different! My results show that there are indeed differences on this basis between the studied contrast medium molecules. The incorporation of two tertiary methyl groups do not significantly increase the questioned rotational barriers.

That no higher chemotoxicity is observed in clinical practice, as they claim, is difficult to prove. Indeed extremely large patient series of prospective, double-blind randomized and indeed comparative studies will be needed to prove a difference between the clinically used products. One homogeneous series of the same product is not very useful for this purpose. The same remark holds for the mentioned iobitridol-elastase study [6]. I doubt that there will ever be such a large study comparing all these monomers. For this reason, I believe that objective chemical parameters permitting differentiation between similar molecules are useful in making the choice of a contrast medium in a clinical setting.

I beg to differ with Carrupt and Testa about their conclusions. Indeed, differences were shown to exist between the monomers and iobitridol was no better than others, of course within the limits of the study as stated in my paper.

Yours etc.,

D Violon

L. Vissenaekenstraat 50, 2600 Berchem-Antwerp, Belgium

Received for publication . Accepted for publication December 3, 2002.

References

1. Violon D. Stabilization of the hydrophilic sphere of non-ionic monomers: are all protected in a similar way? Br J Radiol 2001;74:1097–102.[Abstract/Free Full Text]
2. Meyer D, Fouchet MH, Petta M, Carrupt PA, Gaillard P, Testa B. Stabilization of the hydrophilic sphere of iobitridol, an iodinated contrast agent, as revealed by experimental and computational investigations. Pharm Res 1995;12:1583–991.[CrossRef][Medline]
3. Webster's Concise Dictionary of the English Language. Naples, FL: Trident Press International, 1997.
4. Bonnemain B, Meyer D, Schaeffer M, Dugast-Zrihen M, Legreneur S, Doucet D. New iodinated low-osmolar contrast media: a revised concept of hydrophilicity. Invest Radiol 1990;25:S104–6.
5. Young DC. Computational Chemistry. A practical guide for applying techniques to real-world problems. New York: John Wiley and Sons, Inc. 2001.
6. Prangé T, Neuman A, Corot C, Meyer D. Study of the complex between the contrast agent iobitridol (Xenetix) and elastase (PPE): a model for hydrophobic site protection in drug-protein interactions. Pharm Res 1997;14:1713–7.[CrossRef][Medline]

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