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Where Wi's are the weighting factors specified for each data point. The results presented in Table I and Figures 2 and 3 represent an objective function with Wi 1 for all data points. If one wishes to place more weight on the early time data, the corresponding Wi for early time experimental points could be set at a higher value for example 5 ; . In such a case the optimized parameters would result in very accurate prediction in the early stages at the expense of a loss in accuracy of the predicted concentrations in the late stages and depakote.
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ACKNOWLEDGMENTS This study was supported in part by Public Health Service grants GM 28427 and GM 2587 from the National Institutes of Health. LITERATURE CITED 1. Appel, G. B., and H. C. New. 1977. The nephrotoxicity of antimicrobial agents. N. Engl. J. Med. 296: 784-787. 2. Ascher, N. L., R. L. Simmons, S. Macher, and J. S. Naarian. 1978. Listeria infection in transplant patients. Arch. Surg. 113: 90-94. 3. Avram, M. M., S. R. Nair, H. I. Lipner, and C. E. Cherubin. 1978. Persistent nocardemia following renal transplantation. J. Am. Med. Assoc. 239: 2779-2780. 4. Bekersky, I., and W. A. Colburn. 1980. Acetylation of sulfisoxazole by isolated perfused rat kidney. J. Pharm. Sci. 69: 1359. 5. Bratton, A. C., and E. K. Marshall, Jr. 1939. A new coupling component for sulfanilamide determination. J. Biol. Chem. 128: 537-550. 6. Cohen, M. L., E. B. Weiss, and A. P. Monaco. 1971. Successful treatment of Pneumocystis carinii and Nocardia asteroides in a renal transplant patient. Am. J. Med. 50: 269-276. 7. Jung, D., and S. 0ie. 1980. "High pressure" liquid chromatography of sulfisoxazole and N4-acetylsulfisoxazole in body fluids: Clin. Chem. NY ; 26: 51-54. 8. Jung, D., and S. 0ie. 1981. Decreased in vivo acetylation of sulfisoxazole in the rabbit in the presence of 4-N-acetylsulfisoxazole. Int. J. Pharm. 7: 179-188. 9. 0ie, S. 1981. Effect of 4N-acetyl-sulfisoxazole on the disposition of sulfisoxazole in the rat. Int. J. Pharm. 3: 311-318. 9a.0ie, S. 1985. Pharmacokinetics of sulfisoxazole in rabbits with experimental renal failure after single and multiple dosing. Int. J. Pharm. 23: 345-355. 10. 0ie, S., J. G. Gambertoglio, and L. Fleckenstein. 1982. Comparison of the disposition of total and unbound sulfisoxazole after single and multiple dosing. J. Pharmacokinet. Biopharm. 10: 157-172. 11. Reidenberg, M. M., H. Kostenbauder, and W. P. Adams. 1969. Rate of drug metabolism in obese volunteers before and after starvation and in azotemic patients. Metabolism 18: 209-213. 12. Rieder, J. 1972. Quantitative determination of the bacteriostatically active fraction of sulfonamides and the sum of their inactive nietabolites in the body fluids. Chemotherapy 17: 1-21. 13. Windholz, M. ed. ; . 1976. The Merck index, p. 1160. Merck & Co., Inc., Rahway, N.J. 14. Yacobi, A., and G. Levy. 1977. Intraindividual relationships between serum protein binding of drugs in normal human subjects, patients with impaired renal function, and rats. J. Pharm. Sci. 66: 1285-1288 and diazepam and climara, for example, climara medication.
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