Summary
Previous studies have suggested that the absorption of L-dopa in the elderly Parkinsonian patient might be unusually efficient. In the present investigation, the systemic availability of L-dopa was examined in 5 elderly Parkinsonian patients (mean age=77 years) and 6 young, healthy volunteers (mean age=26 years) following a single oral 300 mg dose of L-dopa. Quantitation of plasma levels of intact L-dopa was effected by ion-exchange column chromatography and spectrofluorimetry. The L-dopa plasma concentration-time profiles obtained confirmed the considerable intersubject variability in the absorption of L-dopa previously reported in the literature. Maximum plasma concentrations of L-dopa generally occurred within 60 min of administration of the dose. The existence of more than one plasma peak of L-dopa concentration was displayed in 45% of the subjects studied. This characteristic was not confined exclusively to either subject group. There was a significantly larger (P<0.02) area under the plasma L-dopa concentration-time curve (AUC ∞o ) in the elderly Parkinsonian patients (mean=234.69 µg · min/ml; SD=84.70) compared to the young, healthy volunteers (mean=82.33 µg · min/ml; SD=31.00). A significant (P<0.01) correlation existed between AUC ∞o and age (r=0.7970; n=11) among the subjects studied. The apparent elimination phase plasma half-life of L-dopa in the elderly Parkinsonian patients (mean=66.0 min; SD=11.1) was not significantly different to that observed in the young, healthy volunteers (mean=74.0 min; SD=18.1). These results suggest that there may be an age-related alteration to the disposition of orally administered L-dopa in the elderly Parkinsonian patient.
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References
Abrams, W. B., Coutinho, C. B., Leon, A. S., Spiegel, H. E.: Absorption and metabolism of levodopa. J. Am. Med. Assoc.218, 1912–1914 (1971)
Bianchine, J. R., Rivera-Calimlim, L., Morgan, J. P., Dujovne, C. A., Lasagna, L.: Metabolism and absorption of L-3, 4-dihydroxyphenylalanine in patients with Parkinson's disease. Ann. N. Y. Acad. Sci.179, 126–140 (1971)
Bianchine, J. R., Sunyapridakul, L.: Individualization of levodopa therapy. Med. Clin. North. Am.58, 1071–1081 (1974)
Broe, G. A., Caird, F. I.: Levodopa for Parkinsonism in elderly and demented patients. Med. J. Aust.1, 630–635 (1973)
Chiou, W. L.: Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level-time curve. J. Pharmacokinet. Biopharm.6, 539–546 (1978)
Cotler, S., Holazo, A., Boxenbaum, H. G., Kaplan, S. A.: Influence of route of administration on physiological availability of levodopa in dogs. J. Pharm. Sci.65, 822–827 (1976)
Curzon, G., Kantamaneni, B. D., Trigwell, J.: A method for the determination of Dopa and 3-O-methyldopa in the plasma of parkinsonian patients. Clin. Chim. Acta37, 335–341 (1972)
Dixon, W. J., Massey, J. J.: Correlation problems. In: Introduction to statistical analysis, pp. 202–216. Tokyo: McGraw-Hill Kogakusha 1969
Dunner, D. L., Goodwin, F. K., Brodie, H. K. H., Spiegel, H. E.: Plasma DOPA response to levodopa administration in man: Effects of a peripheral decarboxylase inhibitor. Clin. Pharmacol. Exp. Ther.12, 212–216 (1971)
Geissbuehler, F.: Méthode de dosage fluorométrique de la DOPA plasmatique à des taux submicromolaires. Clin. Chim. Acta45, 423–427 (1973)
Gibaldi, M., Perrier, D.: In: Pharmacokinetics, J. Swarbrick, (ed.), pp. 293–296. New York: Marcel Dekker 1975
Goldstein, A.: The two sample rank test: A simple alternative to the t-test. In: Biostatistics: An introductory text, pp. 55–58. New York: Macmillan 1964
Grad, B., Wener, J., Rosenberg, G., Wener, S. W.: Effects of levodopa therapy in patients with Parkinson's disease: Statistical evidence for reduced tolerance to levodopa in the elderly. J. Am. Geriatr. Soc.22, 489–494 (1974)
Granerus, A. K., Jagenburg, R., Rodjer, S., Svanborg, A.: Absorption of L-phenylalanine and L-dopa with reference to age. In: Proceedings 4th European symposium on basic research in gerontology, A Vridite (ed.), p. 84 (Abstract) 1973
Granerus, A. K., Jagenburg, R., Rodjer, S., Svanborg, A.: Variations in L-dopa absorption. Acta Med. Scand.196, 459–463 (1974)
Granerus, A. K., Steg, G., Svanborg, A.: Clinical analyses of factors influencing L-Dopa treatment of the parkinsonian syndrome. Acta Med. Scand.192, 1–11 (1972)
Kuruma, I., Bartholini, G., Tissot, R., Pletscher, A.: The metabolism of 3-O-methyldopa, a precursor of DOPA in man. Clin. Pharmacol. Ther.12, 678–682 (1971)
Mearrick, P. T., Graham, G. G., Wade, D. N.: The role of the liver in the clearance of L-Dopa from plasma. J. Pharmacokinet. Biopharm.3, 13–23 (1975)
Mearrick, P. T., Wade, D. N., Birkett, D. J., Morris, J.: Metoclopramide, gastric emptying and L-Dopa absorption. Aust. N. Z. J. Med.4, 144–148 (1974)
Rivera-Calimlim, L., Dujovne, C. A., Morgan, J. P., Lasagna, L., Bianchine, J. R.: L-dopa absorption and metabolism by the human stomach. Pharmacologist12, 269 (Abstract) (1970a)
Rivera-Calimlim, L., Dujovne, C. A., Morgan, J. P., Lasagna, L., Bianchine, J. R.: L-dopa treatment failure: Explanation and correction. Br. Med. J.4, 93–94 (1970b)
Rivera-Calimlim, L., Morgan, J. P., Dujovne, C. A., Bianchine, J. R., Lasagna, L.: L-dopa absorption and metabolism by the human stomach. J. Clin. Invest.49, 79a (Abstract) (1970c)
Shindo, H., Komai, T., Kawai, T.: Studies on the metabolism of D- and L-isomers of 3,4-dihydroxyphenylalanine (DOPA). V. Mechanism of intestinal absorption of D-and L-DOPA-14C in rats. Chem. Pharm. Bull.9, 2031–2038 (1973)
Tyce, G. M., Muenter, M. D., Owens, C. A.: Dihydroxyphenylalanine (Dopa) in plasma during dopa treatment of patients with Parkinson's disease. Mayo Clin. Proc.45, 438–443 (1970)
Vignalou, J., Beck, H.: La L-dopa chez 122 Parkinsoniens de plus de 70 ans. Gerontol. Clin.15, 50–64 (1973)
Wade, D. N., Mearrick, P. T., Birkett, D. J., Morris, J.: Variability of L-dopa absorption in man. Aust. N. Z. J. Med.4, 138–143 (1974)
Wade, D. N., Mearrick, P. T., Morris, J. L.: Active transport of L-dopa in the intestine. Nature242, 463–465 (1973)
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Evans, M.A., Triggs, E.J., Broe, G.A. et al. Systemic availability of orally administered L-dopa in the elderly Parkinsonian patient. Eur J Clin Pharmacol 17, 215–221 (1980). https://doi.org/10.1007/BF00561903
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DOI: https://doi.org/10.1007/BF00561903