Effect of Antiepileptic Drugs on Plasma Lipids,Lipoprotein (a),and Liver Enzymes

Abstract

We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P < .05). The mean pretreatment lipid levels among the groups were not significantly increased. The mean lipoprotein (a) levels were significantly increased in all groups at 3, 6, and 12 months of the treatment period (P < .05). The increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at 3, 6, and 12 months was statistically significant in group 1 (P < .05). The higher levels in lipoprotein (a) (mean > 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70—74).

Get full access to this article

View all access options for this article.

References

Reynolds EH : Chronic antiepileptic toxicity: A review. Epilepsia 1975;16:319—352.

Matsuda I. , Higashi A. , Inotsume N. : Physiologic and metabolic aspects of anticonvulsants. Pediatr Clin North Am 1989;36: 1099—1109.

Franzoni E. , Govoni M. , D'Addato S. , et al: Total cholesterol, high-density lipoprotein cholesterol and triglycerides in children receiving antiepileptic drugs. Epilepsia 1992;33:932—935.

Garcia RE , Moodie DS : Routine cholesterol surveillance in childhood. Pediatrics 1989;84:751—755.

Kark JD , Sandholzer C. , Friedlander Y. , et al: Plasma Lp(a), apolipoprotein (a) isoforms and acute myocardial infarction in men and women: A case-control study in the Jerusalem population . Atherosclerosis 1993;98:139—151.

Aynaci FM , Orhan F. , Orem A. , et al: Effect of antiepileptic drugs on plasma lipoprotein (a) and other lipid levels in childhood. J Child Neurol 2001;16:367—369.

Verrotti A. , Basciani F. , Domizio S. , et al: Serum lipids and lipoproteins in patients with antiepileptic drugs. Pediatr Neurol 1998;19:364—367.

Schwaninger M. , Ringleb P. , Annecke A. , et al: Elevated plasma concentrations of lipoprotein (a) in medicated epileptic patients. J Neurol 2000;247:687—690.

Tumer L. , Serdaroglu A. , Hasanoglu A. , et al: Plasma homocysteine and lipoprotein (a) levels as risk factors for atherosclerotic vascular disease in epileptic children taking anticonvulsants . Acta Paediatr 2002;91:923—926.

10.

Brämswig S. , Sudhop T. , Luers C. , et al: Lipoprotein (a) concentration increases during treatment with carbamazepine. Epilepsia 2003;44:457—460.

11.

Hobbs HH , White AL : Lipoprotein (a) intrigues and insights. Curr Opin Lipidol 1999; 10: 225—236.

12.

Erem C. , Deger O. , Bostan M. , et al: Plasma lipoprotein (a) concentrations in hypothyroid, euthyroid and hyperthyroid subjects. Acta Cardiol 1999 ;54:77—81.

13.

Eiris-Punal J. , Del Rio-Garma M. , Del Rio-Garma MC , et al: Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism . Epilepsia 1999;40:1761—1766.

14.

Isojarvi JI , Laatikainen TJ , Pakarinen AJ , et al: Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993;329:1383—1388.

15.

Isojarvi JI , Laatikainen TJ , Knip M. , et al: Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol 1996;39:579—584.

16.

Isojarvi JI , Rathya J. , Myllyla VV , et al: Valproate, lamotrigine and insulin mediated risks in women with epilepsy. Ann Neurol 1998;43:446—451.

17.

Conover CA , Lee PD , Kanaley JA , et al: Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans. J Clin Endocrinol Metab 1992; 74:1355-1360.

18.

Sing A. , Hamilton-Fairley D. , Koistinen R. , et al: Effect of insulin-like growth factor type-1 (IGF-1) and insulin on the secretion of sex hormone binding globulin and IGF-1 binding protein (IBP-1) by human hepatoma cells. J Endocrinol 1990; 124: R1—R3.

19.

Dahlen G. , Slunga L. , Lindblom B. : Importance of LP(a) lipoprotein and HLA genotypes in atherosclerosis and diabetes . Clin Genet 1994;46:46—51.

20.

Dahlen GH : Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis 1994;108:111—126.

21.

Mackinnon LT , Hubinger L. , Lepre F. : Effects of physical activity and diet on lipoprotein (a). Med Sci Sports Exerc 1997 ;29: 1429—1436.

22.

Eiris JM , Lojo S. , Del Rio MC , et al: Effects of long-term treatment with antiepileptic drugs on serum lipid levels in children with epilepsy. Neurology 1995;45:1155—1157.

23.

Heldenberg D. , Harel S. , Holtzman M. , et al: The effect of chronic anticonvulsant therapy on serum lipids and lipoproteins in epileptic children. Neurology 1983;33:510—513.

24.

Reddy MN : Effect of anticonvulsant drugs on plasma total cholesterol, high-density lipoprotein cholesterol, and apolipoproteins A and B in children with epilepsy. Proc Soc Exp Biol Med 1985;180:359—363.

25.

Utermann G. , Menzel HJ , Kraft HG , et al: Lp(a) glycoprotein phenotypes. Inheritance and relation to Lp(a)-lipoprotein concentrations in plasma. J Clin Invest 1987;80:458—465.

26.

O'Neill B. , Callaghan N. , Stapleton M. , Molloy W. : Serum elevation of high density lipoprotein (HDL) cholesterol in epileptic patients taking carbamazepine or phenytoin. Acta Neurol Scand 1982;65:104—109.

27.

Yalcin E. , Hassanzadeh A. , Mawlud K. : The effects of long-term anticonvulsive treatment on serum lipid profile. Acta Paediatr Jpn 1997;39:342—345.

28.

Zeitlhofer J. , Doppelbauer A. , Tribl G. , et al: Changes of serum lipid patterns during long-term anticonvulsive treatment. Clin Invest 1993;71:574—578.