Summary
Phenylketonuria is an autosomal recessive disorder characterized by elevated concentrations of phenylalanine. Elevated phenylalanine concentrations can impair intellectual functions and the disease is treated with a lifelong diet and frequent monitoring of plasma phenylalanine concentrations. Previous in vitro studies have demonstrated the feasibility of iontophoretically enhanced transdermal transport of phenylalanine. Here we evaluate the feasibility of transdermal iontophoretic extraction of phenylalanine in vivo. Phenylalanine was iontophoretically extracted from the skin of healthy volunteers and of patients with phenylketonuria for up to 6 h and concentrations were compared with those measured in plasma. The amount of phenylalanine iontophoretically extracted from the skin declined over time, suggesting contribution of phenylalanine from the skin in the initial extraction. Phenylalanine iontophoretically extracted from skin correlated with plasma phenylalanine levels at plasma levels above 300 μmol/L. This correlation supports the feasibility of iontophoretic phenylalanine extraction for monitoring phenylketonuria.
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Degim IT, Ilbasmis S, Dundaroz R, Oguz Y (2003) Reverse iontophoresis: a non-invasive technique for measuring blood urea level. Pediatr Nephrol 18(10): 1032-1037.
Delgado-Charro MB, Guy RH (2003) Transdermal reverse iontophoresis of valproate: a noninvasive method for therapeutic drug monitoring. Pharm Res 20(9): 1508-513.
Huang T, Warsinke A, Kuwana T, Scheller FW (1998) Determination of l-phenylalanine based on an NADH-detecting biosensor. Anal Chem 70(5): 991-97.
Li SK, Higuchi WI, Zhu H, Kern SE, Miller DJ, Hastings MS (2003) In vitro and in vivo comparisons of constant resistance AC iontophoresis and DC iontophoresis. J Control Release 91(3): 327-43.
Longo N (2004) Inherited disorders of amino acid metabolism presenting in adults. In: Kasper D, Braunwald E, Fauci A, et al, eds. Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 2331–2334.
Mackey SA, Berlin CM Jr (1992) Effect of dietary aspartame on plasma concentrations of phenylalanine and tyrosine in normal and homozygous phenylketonuric patients. Clin Pediatr (Phila) 31(7): 394-99.
Merino V, Lopez A, Hochstrasser D, Guy RH (1999) Noninvasive sampling of phenylalanine by reverse iontophoresis. J Control Release 61(1–2): 65-9.
Potts RO, Tamada JA, Tierney MJ (2002) Glucose monitoring by reverse iontophoresis. Diabetes Metab Res Rev 18(Supplement 1): S49-3.
Schweitzer-Krantz S, Burgard P (2000) Survey of national guidelines for the treatment of phenylketonuria. Eur J Pediatr 159(Supplement 2): S70-3.
Surtees R, Blau N (2000) The neurochemistry of phenylketonuria. Eur J Pediatr 159(Supplement 2): S109-13.
Yan G, Higuchi WI, Szabo A, Li SK (2004) Correlation of transdermal iontophoretic phenylalanine and mannitol transport: test of the internal standard concept under DC iontophoresis and constant resistance AC iontophoresis conditions. J Control Release 98(1): 127-38.
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Communicating editor: Michael Gibson
Competing interests: None declared
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Longo, N., Li, S.K., Yan, G. et al. Noninvasive measurement of phenylalanine by iontophoretic extraction in patients with phenylketonuria. J Inherit Metab Dis 30, 910–915 (2007). https://doi.org/10.1007/s10545-007-0675-y
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DOI: https://doi.org/10.1007/s10545-007-0675-y