Significance of Increased Serum Gamma-Glutamyltransferase Activity during Long-Term Anticonvulsive Treatment. Clinical and Experimental Studies^1,2

Abstract

Significance of increased serum gamma-glutamyltransjerase activity during long-term anticonvulsive treatment. Clinical and experimental studies. Neuropadiatrie 6: 77-89 (1975). In epileptic children on anticonvulsive treatment for at least 4 weeks, the following laboratory tests were performed and compared to age matched controls: serum activity determinations of gamma-glutamyltransferase (GGT), alanine (GPT) and aspartate aminotransferases, leucin arylamidase (LAP), alkaline phosphatase (AP), glutamate dehydrogenase (GLDH), and cholinesterase (CHE), determinations of fibranogen and clotting factors II, V, and VII, and of urinary D-glucaric acid excretion. Serum GGT activity was increased up to about 10 times above the upper limit of normal range (x + 2s) in 83 of 103 children, AP was enhanced in 26, CHE in 21, GLDH in 20, and GPT in 14 children (p< .05). Except for AP, the frequency of other increased serum activities was raised according to the degree of GGT enhancement. Clotting factor V was moderately elevated in 21°/o of those children, who had enhanced GGT activities (p < .05), no further significant deviation of any of the clotting factors was observed. In 17 children so studied the serum GGT activity was closely correlated to the urinary excretion of D-glucaric acid, an indicator of microsomal enzyme activity (r= + 0.67, p < .01). In phenytoin treated rats, given 100 mg/kg and 300 mg/kg, respectively, daily for 17-25 days, a dose dependent enhancement of liver and serum GGT was measured. This occured predominantly in total liver and in liver microsomes, less marked in the soluble liver fraction and in serum. An elevation of microsomal cytochrome P-450 in the liver was also found. It is concluded, that isolated enhancement of serum GGT activity during anticonvulsive treatment is not indicative of liver damage, but rather, of a clinically insignificant elevation of microsomal enzymes. Increased blood levels of other so-called liver enzymes and of clotting factors may be suggestive of more complex alterations of liver metabolism, the pattern of the laboratory findings being indicative of a clinically latent disturbance of excretory functions of the hepatobiliary system rather than of hepatic parenchymal damage. Enhancement of serum AP activity is primarily due to a disturbance in calcium metabolism.

Microsomal enzyme induction in children: the influence of carbamazepine treatment on antipyrine kinetics, 6 beta‐hydroxycortisol excretion and plasma gamma‐glutamyltranspeptidase activity.

“…In addition there was no sigcn nificant correlation between the percent change in y-glutamyltranspeptidase activity and the per cent change in antipyrine clearance. Serum y-glutamyltranspeptidase in two groups of epileptic children >,, g receiving various anticonvulsant drugs have been -0 reported to be considerably higher than in children v receiving no drug therapy (Bartels et al, 1975;de Park, 1979). Branch & Shand (1979) proposed that >,.j hepatic drug clearance may be regarded as a product of liver size and specific drug metabolising enzyme activity per unit mass of liver and that larger responses to inducing agents would be expected in vindividuals with large livers.…”

“…Enzyme induction has also been assessed by measuring changes in the disposition of endogenous compounds. Plasma y-glutamyltranspeptidase (yGT) activity is elevated in groups of young epileptics receiving anticonvulsant drugs (Bartels, et al, 1975;de Wolff et al, 1980) but the influence of CBZ monotherapy on -y-glutamyltranspeptidase activity in individual children is unknown.…”

Effects of Anticonvulsive Drugs on the Activity of Gammaglutamyltransferase and Aminotransferases in Serum

“…It has previou sl y been sho w n (3,5 -10,28) that antico nvulsive treatment influences the activity of GGT. Several authors reg ard GGT as one indicator of hepatic enzym e induction (3,(5)(6)(7)30) . This enzyme is not specific for the liver, but isoenzyme patterns have suggested that the so urce of serum activities of GGT during a ntico nvulsive treatment is hepatic tissue (9) ; it does not correlate with the activity of alkaline phosphata se (1,26,3 I).…”

“…The results indi-Patients on long-term therapy with anticonvulsive drugs may have elevated serum levels of transferases 0-10). During the last decade, debate has focused attention on whether these high enzyme activities are the expression of purely microsomal enzyme induction or of additional liver cell damage [0][1][2][3][4][5]7,8,11), but even morphological studies on small numbers of patients (2,12,13,13a) have not resolved this important clinical problem.We have occasionally observed clinically significant liver disease, although elevated transferases in serum of children receiving anticonvulsive therapy were more common. In addition, increased numbers of cytolysosomes (4) have been found by…”

“…The results indi-Patients on long-term therapy with anticonvulsive drugs may have elevated serum levels of transferases 0-10). During the last decade, debate has focused attention on whether these high enzyme activities are the expression of purely microsomal enzyme induction or of additional liver cell damage [0][1][2][3][4][5]7,8,11), but even morphological studies on small numbers of patients (2,12,13,13a) have not resolved this important clinical problem.…”