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  4. Deposition and retention of radiolabeled serum constituents in hair after systemic administration

Deposition and retention of radiolabeled serum constituents in hair after systemic administration

Stout, P., Dehn, D., & Ruth, JA. (1998). Deposition and retention of radiolabeled serum constituents in hair after systemic administration. Drug Metabolism and Disposition, 26(9), 900-906.

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Abstract

To investigate the chemical mechanisms involved in the accumulation of drugs or other compounds in hair, we examined the deposition of radiolabeled serum constituents in the hair of BALB/c (albino) and C57 (pigmented) mice. The extents of in vivo incorporation of a normal serum cation (Ca-45(2+)), a serum anion (Cl-36(-)), a neutral constituent ([C-14]urea), and a structural component of hair ([S-35]cysteine) were studied to provide a reference framework for the examination of foreign substances deposited in hair from serum. The use of two mouse strains allowed evaluation of the effect of hair pigmentation on levels of accumulation. Additionally, the endogenous contents of Mg2+, Na+, and K+ (measured by inductively coupled plasma-atomic emission spectroscopy) were determined, as was their stability to removal. Hair concentrations of isotopes were calculated from mean specific activities determined over the treatment period and corrected for quenching and decay. Ca-45(2+) accumulation (500 ng/mg of hair in C57 mice and 25 ng/mg of hair in BALB/c mice) was unaffected by 24-hr phosphate buffer extraction. Of the [C-14]urea accumulated (3500 ng/mg in C57 and BALB/c mice), 50% was removed by 24-hr extraction in phosphate buffer. Of the Cl-36(-) accumulated (65 ng/mg in 057 mice and 30 ng/mg in BALB/c mice), one half was removed by 24-hr extraction in phosphate buffer. The accumulated [S-35]cysteine (210 ng/mg in 057 mice and 110 ng/mg in BALB/c mice) could not be removed, Endogenous Mg2+ (350 ng/mg in 057 mice and 75 ng/mg in BALB/c mice) was stable to 24-hr extraction with phosphate buffer. K+ (2500 ng/mg) and Na+ (400 ng/mg) concentrations were approximately equal in the two strains and were largely extractable. Based on the accumulation of a neutral serum constituent (urea), the data suggest that factors other than ionic binding are important in the deposition of circulating molecules into hair. The extent and reversibility of ionic binding are dependent on the chemical nature of the binding substance. The presence of hair pigmentation greatly increased the accumulation of Ca-45(2+), Cl-36(-), and [S-35]cysteine. These data suggest a multi-compartmental nature of drug storage in hair

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