Quantitative investigation of copper(II) and zinc(II) complexes with S-carboxymethyl-L-cysteine and computer-simulated appraisal of their potential significance in vivo.
S-carboxymethyl-L-cysteine (SCC) is a mucolytic agent extensively used in the treatment of respiratory tract disorders. Some of the undesirable side effects observed during SCC therapy being reminiscent of symptoms characteristic of copper and zinc imbalances, the objective of this paper was to test the possible interference of SCC with the metabolism of these two metals. Copper(II)- and zinc(II)-SCC complex equilibria have thus been investigated under physiological conditions by means of classical potentiometry combined with computer-assisted calculation techniques. Formation constants derived from these studies have then been used to simulate 1) the potential influence of SCC on the distribution of the above metals in blood plasma and 2) the extent to which gastrointestinal interactions between the drug and each metal ion in turn are likely to affect the bioavailability of each other. The results of these simulations show that 1) plasma therapeutic levels of SCC are not likely to induce dramatic changes in the distributions of copper(II) and zinc(II) low molecular weight fractions, 2) the gastrointestinal distribution of the drug is not affected by standard dietary doses of these metals, and 3) in contrast, therapeutic concentrations of SCC are capable of mobilizing significant fractions of both metals into tissue-diffusible electrically neutral complexes. In conclusion significant depletions of neither copper nor zinc are to be expected from oral administration of SCC. While the drug may to some extent facilitate the excretion of Cu2+ and Zn2+ ions from blood plasma, its gastrointestinal influence is, on the contrary, favorable to a better absorption of these two metals.
Brumas
V
V
Department of Chemistry, INSERM Unité 305, Université Paul Sabatier, Toulouse, France.
Venturini
M
M
Filella
M
M
Berthon
G
G
D000042:Absorption; D001682:Biological Availability; D002233:Carbocysteine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D003198:Computer Simulation; D003300:Copper / Q000097:blood / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives*; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011199:Potentiometry; D015032:Zinc / Q000097:blood / Q000378:metabolism*
D002233:Carbocysteine; D003300:Copper; D015032:Zinc; D003545:Cysteine