QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Everts, H. B. Articles by Canolty, N. L. Search for Related Content PubMed PubMed Citation Articles by Everts, H. B. Articles by Canolty, N. L.

A Compartmental Model Predicts That Dietary Potassium Affects Lithium Dynamics in Rats^1,2,3,

Department of Foods and Nutrition, University of Georgia, Athens, GA 30602 ^* Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348

Lithium is the treatment of choice for manic depression, but therapy often results in nephrogenic diabetes insipidus and lithium intoxication. To investigate the effects of dietary potassium on potential side effects of lithium therapy, a mathematical model was built using the modeling program SAAM (Simulation, Analysis, And Modeling). Experimental data modeled were from adult male Sprague-Dawley rats fed diets with or without lithium and one of three levels of potassium for 17 d. A five-compartment model of lithium dynamics was built that was consistent with data from rats fed a lithium-containing diet adequate in potassium. This model was then compared with data from rats fed the other two lithium-containing diets. The model predicts that both the fractional transfer coefficient and rate of transport of lithium to the serum compartment from the kidney compartment are lower in rats fed the potassium-adequate diet than in those fed the potassium-deficient diet, and even lower in those fed the potassium-supplemented diet. In addition, fractional transfer coefficients into the serum compartment from the sampled and simulated tissue compartments changed differently with time depending on the amount of dietary potassium. The model also predicts that there would be less accumulation of lithium in the kidney, sampled tissue and simulated tissue compartments with supplemental dietary potassium. The model suggests that potassium supplementation, after a 7-d delay, protects against nephrogenic diabetes insipidus and the potentially toxic accumulation of lithium by decreasing the reabsorption of lithium from the kidneys and increasing lithium efflux from the tissues.

KEY WORDS: • lithium dynamics • potassium • compartmental analysis • rats • mathematical modeling

¹ The compartmental analysis in this paper was described in a thesis [Everts, H. B. (1995) A Compartmental Analysis of the Effects of Dietary Potassium on the Turnover of Lithium in Rats. Master's thesis, The University of Georgia, Athens, GA] and presented in part at Experimental Biology 95, Atlanta, GA [Everts, H. B., Jang, H.-K., Boston, R. C. & Canolty, N. L. (1995) Compartmental analysis of dietary potassium and lithium turnover in rats. FASEB J. 9: A465 (abs.)]; the experimental work on which the compartmental analysis was based was described in a dissertation [Jang, H.-K. (1992) Lithium-Sodium-Potassium Interactions and Water Balance in Adult Rats. Doctoral thesis, The University of Georgia, Athens, GA] and presented in part at the Annual Meeting of the Federation of American Societies for Experimental Biology, April 1992, Anaheim, CA [Jang, H.-K. and Canolty, N. L. (1992) Potassium and sodium interactions with lithium in adult rats. FASEB J. 6: A1947 (abs.)].

² Supported by Georgia Agricultural Experiment Station Project GE000746.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

Manuscript received 28 July 1995. Revision accepted 16 January 1996.