PharmPK Discussion - Toxicity of deoxyinosine as modulating agent of 5-FU activation

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On 23 Sep 1998 at 11:01:24, Catalin Jacques (jacques.catalin.at.pharmacie.univ-mrs.fr) sent the message


Dear All,

Various biomodulators have been extensively tested for decades to enhance
cytotoxicity of 5-FU and other fluoropyrimidines.
Among them, deoxyinosine is a promosing modulator involved in thymidine
phosphorylase (TP) activity, a key enzyme in the activation pathway of 5-FU
into active deoxynucleotides metabolites.
Results as reported in the literature showed that deoxyinosine
significantly mediates the in vitro sensitivity of various human carcinoma
lines to 5-FU, which has been correlated by our own results.
Surprisingly, deoxyinosine doesn't seem to have been tested in vivo,
despite the fact that this modulator is known to be potent since the
earlies 70's.
Does anybody have information about a possible in vivo toxicity of this drug=
?
Or does anyone have infos about un-published clinical use of the
association deoxyinosine/5-FU?

Any information is much welcome.

Pr. Jacques Catalin
Laboratoire de Toxicocin=E9tique et Pharmacocin=E9tique
Facult=E9 de Pharmacie
27, Bd Jean Moulin
13385 Marseille cedex 05
France

Tel: (33) (0)4 91 83 55 09
Fax: (33) (0)4 91 83 56 67

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