Abstract
The serum activity of gammaglutamyltransferase (GGT) and the urinary excretion of D-glucaric acid (DGA) are significantly enhanced in patients treated with enzyme inducing drugs. However, quantitative data on the correlation between drug dose and increase of these indicators of enzyme induction are sparce and contradictory. The question to be answered by the present study was: Are GGT and DGA measurements suitable to assess the inducing properties of an individual anticonvulsant drug quantitatively? Children on constant single medication for at least two months with primidone (PR), carbamazepine (CBZ) or sodium valproate (VAL) were investigated. DGA was measured colorimetrically, phenobarbital (PB) and CBZ by EMIT, VAL by GC, GGT and Creatinine by standard methods. There was a significant (p<.001) positive correlation between the drug dose and the excretion of DGA for all three anti-convulsants studied. The enhancement of DGA by VAL was less pronounced than by PR and CBZ. DGA excretion was closely (p<.001) correlated to the serum levels of VAL and PB (from PR), but not of CBZ. DGA excretion was inversely correlated to the level to dose ratio of CBZ, thus reflecting the degree of autoinduction of CBZ breakdown. Except for PR, the data on GGT were, though similar to those on DGA, less conclusive owing to a greater variation of individual values. In conclusion, DGA and GGT are useful quantitative measures of the enzyme inducing properties of PR, CBZ, and VAL. DGA reacts more sensitively and less variably than does GGT. Compared to PR and CBZ, VAL is a relatively weak but distinct enzyme inducing agent. DGA enhancement does not permit to differentiate between autoinduction and heteroinduction.
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Wallis, S., Bartels, H. DOSE DEPENDENT ENZYME INDUCTION IN ANTICONVULSANT TREATED CHILDREN. Pediatr Res 19, 1123 (1985). https://doi.org/10.1203/00006450-198510000-00300
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DOI: https://doi.org/10.1203/00006450-198510000-00300