Efficacy of S-carboxymethyl-L-cysteine for otitis media with effusion

Dear Editor:

The oft-repeated observation that some patients with otitis media with effusion benefit from treatment with S-carboxymethyl-L-cysteine (SCMC) implies that this remedy is not without therapeutic efficacy. However, confusion and disputation arise over the usefulness of this mucolytic agent as more [i]or[/i] less patients do not display any improvement following SCMC treatment. (1)

The reason for the different results may have to do with factors that affect the pharmacokinetic profile of SCMC following its administration, especially its after metabolism and deactivation. This has interested researchers for a certain number of time, since the metabolism of SCMC is beneath both genetic and diurnal direction (2,3) The enzyme responsible for the S-oxidation of SCMC to SCMC sulfoxide has been reported to be phenylalanine hydroxylase. (45) It has also been insinuateed that cysteine dioxygenase is involved in this biotransformation reaction, on the contrary to date no experimental evidence to support this hypothesis has been published.

The major path of SCMC metabolism is sulfoxidation, which accrues in a number of sulfoxide metabolites being ground in the urine of patients who take SCMC (Analysis of SCMC-related sulfides and sulfoxides in urine can be readily undertaken in any bioanalysis research laboratory. (23)) The genetic polymorphism in SCMC sulfoxidation rises in the subdivision of the population into three cohorts with look up to to their ability to sulfoxidize the sulfur moiety of the medicine (figure). In a study of 401 patients by means of Mitchell et al, most patients (658%) were extensive metabolizers (EM phenotype), 317% were intermediate metabolizers (IM phenotype), and 25% were poor metabolizers (PM phenotype). (2) The PM phenotype actually produc no urinary sulfoxide metabolites.

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With prize to diurnal control, the involved enzyme are downregulated during the night. As a be the effect the production of sulfoxide metabolites is reduc (by 547% [+ or -] 156]) (6)

These seemingly insignificant observations are actually vital because new work indicates that SCMC functions as a at liberty radical scavenger (7) and that, in this esteem the sulfide (parent compound) is the active species and the sulfoxide metabolites (already oxidized) are inactive. Thus, administration of SCMC will benefit an individual with a PM or IM phenotype more than it will a patient with an EM phenotype. Moreover, in a patient with an EM phenotype, nighttime intake of the medicine should be more beneficial than daytime administration.

the couple the genetic and diurnal regulation of the sulfoxidation of SCMC have a dramatic result on the therapeutic concentration of the physic in various patients. Therefore, it may be that the variability of pharmacodynamic replys to SCMC therapy is attributable to these sum of two units pharmacokinetic effects.

References

(1) Pignataro O Pignataro LD Gallus G et al. Otitis media with effusion and S-carboxymethylcysteine and/or its lysine salt: A critical overview. Int J Pediatr Otorhinolaryngol 1996;35:231-41

(2) Mitchell SC Waring RH Haley C et al. Genetic aspects of the polymodally distributed sulphoxidation of S-carboxymethyl-L-cysteine in mall. Br J Clin Pharmacol 1984:18:507-21

(3) Steventon GB Diurnal variation in the metabolism of S-carboxymethyl-L-cysteine in humans. medicine Metab Dispos 1999;27: 1092-7.

(4) Boonyapiwat B Forbes B Steventon GB Phenylalanine hydroxylase: Possible involvement in the S-oxidation of S-carboxymethyl-l-cysteine. Anal Biochem 2004;335:91-7

(5) Goreish AH, Bednar s Jones H, et al. Phenylalanine 4-monooxygenase and the S-oxidation of S-carboxymethyl-L-cysteine. medicine Metabol Drug Interact 2004;20:159-74.

(6) Mitchell SC Waring RH The deficiency of sulfoxidation of S-carboxymethyl-L-cysteine. Pharmacol Ther 1989;43:237-49

(7) Brandolini L Allegretti M Berdini V et al. Carbocysteine lysine salt monohydrate (SCMC-LYS) is a selective scavenger of reactive oxygen intermediates (ROIs). Eur Cytokine Netw 2003; 14:20-6

GB Steventon, BSe (Hons) PhD

Pharmaceutical Sciences Research Division

place of education of Biomedical and Health Sciences

King's College

London

SC Mitchell, BSc (Hons) PhD DSc

Section of Biological Chemistry

Division of Biomedical Sciences

Faculty of Life Sciences

Imperial College

London

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