Pharmacokinetics of Lithium in Egyptian Bipolar Patients: Dosage Adjustment Approach

Abdel-Hameed Ibrahim Mohamed Ebid, Dina Awny Tawfik Abd-Allah, Mahmoud Mamdouh Mohamed Elhabiby

Pharmacy Practice Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
Psychiatry Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.

DOI: 10.4236/pp.2014.54052                

Abstract

Due to its proven clinical effectiveness, lithium has been considered as a corner stone for the long-term treatment of Bipolar Disorder (BPD) for more than half a century. The objective of this study was to evaluate the effect of patients’ different co-variables on lithium pharmacokinetics and the development of a pharmacokinetic model for the estimation of lithium clearance in Egyptian bipolar patients; this model can be used afterwards during dosage adjustment to achieve target’s steady-state plasma concentrations in similar settings. The study was conducted on 65 adult Egyptian bipolar patients of both genders, in both the in- and out-patient settings in the Institute of Psychiatry, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Patients’ full profiles were prepared, containing all their data. Single daily dose regimen was followed by all patients and one blood sample was drawn 12 ± 0.5 hours post dose for steady-state lithium concentration, sodium level and serum creatinine determinations. Lithium trough levels were determined using Flame Emission Photometry technique. Data analysis and regression modeling revealed a significant correlation between total body weight (TBW), body surface area (BSA) and lithium clearance. Due to multicollinearity, BSA was excluded from the basic non-linear regression equation and TBW was found to be the only covariate affecting lithium clearance. Mean lithium clearance was found to be 0.243 ± 0.097 Lit/Kg/day, ranging from 0.091 to 0.71 Lit/Kg/day.

Keywords

Lithium; Pharmacokinetics; Bipolar Disorder

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Fonseca, C.P., Montezinho, L.P. and Castro, M.M.C.A. (2012) Li+ in Bipolar Disorder—Possible Mechanisms of Its Pharmacological Mode of Action. In: Barnhill, J., Ed., Bipolar Disorder—A Portrait of a Complex Mood Disorder.
[2]	Bezchlibnyk, Y. and Young, L.T. (2002) The Neurobiology of Bipolar Disorder: Focus on Signal Transduction Pathways and the Regulation of Gene Expression. Canadian Journal of Psychiatry, 47, 135-148.
[3]	Belmaker, R.H. (2004) Bipolar Disorder. New England Journal of Medicine, 351, 476-486. http://dx.doi.org/10.1056/NEJMra035354
[4]	Martinez-Aran, A., et al. (2004) Cognitive Function across Manic or Hypomanic, Depressed, and Euthymic States in Bipolar Disorder. American Journal of Psychiatry, 161, 262-270. http://dx.doi.org/10.1176/appi.ajp.161.2.262
[5]	Goldberg, J.F. and Roy, K.N. (2009) Chengappa, Identifying and Treating Cognitive Impairment in Bipolar Disorder. Bipolar Disorders, 11, 123-137. http://dx.doi.org/10.1111/j.1399-5618.2009.00716.x
[6]	Melchior, M., et al. (2007) Work Stress Precipitates Depression and Anxiety in Young, Working Women and Men. Psychological Medicine, 37, 1119-1129. http://dx.doi.org/10.1017/S0033291707000414
[7]	Hammen, C., Brennan, P.A. and Shih, J.H. (2004) Family Discord and Stress Predictors of Depression and Other Disorders in Adolescent Children of Depressed and Nondepressed Women. Journal of the American Academy of Child & Adolescent Psychiatry, 43, 994-1002. http://dx.doi.org/10.1097/01.chi.0000127588.57468.f6
[8]	American Psychiatric Association (2000) Mood Disorders. In: Diagnostic and Statistical Manual of Mental Disorders: 4th Edition: DSM-IV-TR®, American Psychiatric Association, Arlington.
[9]	Duman, R.S. (2002) Synaptic Plasticity and Mood Disorders. Molecular Psychiatry, 7, S29-S34. http://dx.doi.org/10.1038/sj.mp.4001016
[10]	Cade, J.F. (2000) Lithium Salts in the Treatment of Psychotic Excitement 1949. Bulletin of the World Health Organization, 78, 518-520.
[11]	Baldessarini, R.J., Tondo, L. and Hennen, J. (1999) Effects of Lithium Treatment and Its Discontinuation on Suicidal Behavior in Bipolar Manic-Depressive Disorders. The Journal of Clinical Psychiatry, 60, 77-84; discussion 111-116.
[12]	Malhi, G.S., et al. (2013) Potential Mechanisms of Action of Lithium in Bipolar Disorder. CNS Drugs, 27, 135-153. http://dx.doi.org/10.1007/s40263-013-0039-0
[13]	Grandjean, E.M. and Aubry, J.-M. (2009) Lithium: Updated Human Knowledge Using an Evidence-Based Approach: Part II: Clinical Pharmacology and Therapeutic Monitoring. CNS Drugs, 23, 331-349. http://dx.doi.org/10.2165/00023210-200923040-00005
[14]	Ward, M.E., Musa, M.N. and Bailey, L. (1994) Clinical Pharmacokinetics of Lithium. The Journal of Clinical Pharmacology, 34, 280-285. http://dx.doi.org/10.1002/j.1552-4604.1994.tb01994.x
[15]	Bauer, L.A. (2008) Lithium. In: Applied Clinical Pharmacokinetics, The McGraw-Hill Companies, New York.
[16]	Sproule, B.A., Hardy, B.G. and Shulman, K.I. (2000) Differential Pharmacokinetics of Lithium in Elderly Patients. Drugs & Aging, 16, 165-177. http://dx.doi.org/10.2165/00002512-200016030-00002
[17]	Thornhill, D.P. (1978) Pharmacokinetics of Ordinary and Sustained-Release Lithium Carbonate in Manic Patients after Acute Dosage. European Journal of Clinical Pharmacology, 14, 267-271. http://dx.doi.org/10.1007/BF00560460
[18]	Gai, M.A.N., et al. (2000) Effect of Three Different Diets on the Bioavailability of a Sustained Release Lithium Carbonate Matrix Tablet. International Journal of Clinical Pharmacology and Therapeutics, 38, 320-326. http://dx.doi.org/10.5414/CPP38320
[19]	Prien, R.F. and Caffey, E.M. (1976) Relationship between Dosage and Response to Lithium Prophylaxis in Recurrent Depression. The American Journal of Psychiatry, 133, 567-570.
[20]	Stokes, P.E., Kocsis, J.H. and Arcuni, O.J. (1976) Relationship of Lithium Chloride Dose to Treatment Response in Acute Mania. Archives of General Psychiatry, 33, 1080. http://dx.doi.org/10.1001/archpsyc.1976.01770090070006
[21]	Speirs, J. and Hirsch, S.R. (1978) Severe Lithium Toxicity with “Normal” Serum Concentrations. British Medical Journal, 1, 815. http://dx.doi.org/10.1136/bmj.1.6116.815
[22]	Mitchell, P.B. (2001) Therapeutic Drug Monitoring of Psychotropic Medications. British Journal of Clinical Pharmacology, 52, 45-54. http://dx.doi.org/10.1111/j.1365-2125.2001.00174.x
[23]	Gadallah, M.F., Feinstein, E.I. and Massry, S.G. (1988) Lithium Intoxication: Clinical Course and Therapeutic Considerations. Mineral and Electrolyte Metabolism, 14, 146-149.
[24]	Mosteller, R.D. (1987) Simplified Calculation of Body-Surface Area. The New England Journal of Medicine, 317, 1098. http://dx.doi.org/10.1056/NEJM198710223171717
[25]	Tietz, N.W. (1995) Clinical Guide to Laboratory Tests. WB Saunders Co., Philadelphia.
[26]	Amdisen, A. (1975) Monitoring of Lithium Treatment through Determination of Lithium Concentration. Danish Medical Bulletin, 22, 277-291.
[27]	Lehmann, K. and Merten, K. (1974) Die Elimination von Lithiumin Abhangigkeit vom Lebensalter bei Gesunden und Niereninsuffizienten. International Journal of Clinical Pharmacy, 10, 292-298.
[28]	Reiss, R.A., et al. (1994) Lithium Pharmacokinetics in the Obese. Clinical Pharmacology & Therapeutics, 55, 392-398. http://dx.doi.org/10.1038/clpt.1994.47
[29]	Amdisen, A. (1977) Serum Level Monitoring and Clinical Pharmacokinetics of Lithium. Clinical Pharmacokinetics, 2, 73-92. http://dx.doi.org/10.2165/00003088-197702020-00001
[30]	Platman, S.R. and Fieve, R.R. (1968) Biochemical Aspects of Lithium in Affective Disorders. Archives of General Psychiatry, 19, 659-663. http://dx.doi.org/10.1001/archpsyc.1968.01740120019003