Antiepileptic Drugs: Biotransformation, Metabolism, and Serum Half‐Life

Glazko, Anthony J.

doi:10.1111/j.1528-1157.1975.tb06064.x

Cited by 46 publications

(13 citation statements)

References 88 publications

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“…The established dose of FA may be difficult to establish since some studies have used as little as 100-500 kg (Dansky et al, 1987), while others have used I , 5 . 10, 15, 20, and 30 mg FA (Kutt et al, 1966;Jensen and Olesen, 1970;Andreasen et al, 1971; Baylis et al, 1971;Mattson et al, 1973;Glazko, 1975;Furlanut et al, 1978;Makki et al, 1980;Berg et al, 1983u,b).…”

Section: Increase In Serum Folatementioning

confidence: 99%

Decrease of Serum Folates in Healthy Male Volunteers Taking Phenytoin

et al. 1988

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The effect of phenytoin (PHT) on serum folate and the effect of additional oral folic acid (FA) on serum folate during continued treatment with PHT were studied in 13 healthy male subjects 20-35 years of age. The study was divided into two phases: Phase I determined Vmax (mg/kg/day) and Km (microgram/ml) of PHT in order to calculate the PHT doses needed for the second phase. Phase II was a four-way cross-over study to examine the effect of 1 and 5 mg FA on total serum PHT concentrations 1 microgram/ml less and 5 micrograms/ml greater than the subject's Km, Km-1 and Km+5, respectively. Both phases examined the effect of PHT on serum folate. In Phase I, serum folate decreased by a mean and standard deviation of 42.15 +/- 21.44% after an average of 24.15 +/- 5.63 days of PHT administration, with a mean steady-state total serum PHT concentration of 8.45 +/- 2.70 micrograms/ml. Mean percentage decreases in serum folate before the addition of 1 and 5 mg FA in Phase II were 12.80 +/- 31.45% and 23.24 +/- 21.24% for Km-1 and Km+5, respectively. The average numbers of days of PHT administration and total serum PHT concentrations before FA administration were 9.52 +/- 3.34 and 15.84 +/- 7.02 days, and 2.60 +/- 2.18 and 8.64 +/- 3.44 micrograms/ml, for Km-1 and Km+5, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Increase In Serum Folatementioning

confidence: 99%

Decrease of Serum Folates in Healthy Male Volunteers Taking Phenytoin

et al. 1988

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“…In a study using a Sephadex column to separate the free from the bound ethosuximide concentration, no significant degree of protein binding was identified, although no actual data were provided . This has led to the belief that ethosuximide binding is negligible . The SPC for ethosuximide states that ethosuximide is “not significantly bound.” Using the saliva/serum ratio, an indirect method of determining free serum concentration as it is assumed that serum free levels are in equilibrium with saliva values, ethosuximide binding has been reported to vary from 0% to 5% .…”

Section: Discussionmentioning

confidence: 99%

Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non–protein‐bound concentrations

et al. 2017

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“…This pseudosteady state could result from folate depletion. If folate is a cofactor in PHT metabolism (Maxwell et al, 1972;Glazko, 1975;Labadorios et al, 1978;Driessen et al, 1980;Makki et al, 1980;Berg et al, 1983a), either in formation of epoxide, p-HPPH, diol, catechol, or all measurable metabolites, depletion of folate would cause the time required to reach PHT steady state to be longer than that calculated Abbreviations as in Table 2.…”

Section: Discussionmentioning

confidence: 99%

Phenytoin Pharmacokinetics: Before and After Folic Acid Administration

et al. 1992

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Phenytoin (PHT) exhibits linear and Michaelis-Menten pharmacokinetics. PHT decreases serum folate; the vitamin folic acid (FA) is hypothesized to be a cofactor in the metabolism of PHT. The depletion of serum folate may explain the unpredictability of measured total serum PHT concentrations and time to steady state as compared with the Michaelis-Menten predictive calculations. We examined PHT pharmacokinetics before and after FA supplementation in 13 healthy male volunteers. The study was divided into two phases. Phase I determined V(max) (mg/day) and Km (micrograms/ml) of PHT to calculate PHT doses needed for the second phase. Phase II was a four-way cross-over study to examine the effect of 1 and 5 mg FA on total serum PHT concentrations 1 microgram/ml less and 5 micrograms/ml greater than the subject's Km, Km - 1 and Km + 5, respectively. Predicted versus measured total serum PHT concentrations, t90% (days to steady state), and the effect of FA were calculated for Km - 1 and Km + 5 before and after 1 or 5 mg FA. The measured total serum PHT concentration was always greater than the calculated concentration (p less than 0.05), and t90% was always longer than the calculated t90% (p less than 0.05) for Km - 1 before FA (all subjects decreased serum FA); the same was observed for Km + 5. If folate is assumed to be a cofactor in PHT metabolism, these results are expected, because depletion of the vitamin would indicate less folate to drive the metabolism of PHT, resulting in higher total serum PHT concentrations and longer time to reach steady state.(ABSTRACT TRUNCATED AT 250 WORDS)

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Antiepileptic Drugs: Biotransformation, Metabolism, and Serum Half‐Life

Cited by 46 publications

References 88 publications

Decrease of Serum Folates in Healthy Male Volunteers Taking Phenytoin

Decrease of Serum Folates in Healthy Male Volunteers Taking Phenytoin

Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non–protein‐bound concentrations

Phenytoin Pharmacokinetics: Before and After Folic Acid Administration

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