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  • Book
    edited by Thomas Birch ; with an introduction by Douglas McKie.
    Print Access Request
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    Call Number
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    Books: History - LC Classification (Downstairs)
    v. 1-6, (1772) 1965-66.
    Q113 .B79
    6
  • Article
    Wilson JT, Höjer B, Rane A.
    Clin Pharmacol Ther. 1976 Jul;20(1):48-58.
    Epileptic children were given phenytoin (DPH) in loading (four doses of 4.4 to 6.3 mg/kg/dose given 8-hourly and then 6 mg/kg/day) or conventional (5 to 9 mg/kg/day) doses. Plasma levels of DPH and its main metabolite (p-OH-DPH) were measured by a mass fragmentographic technique. Plasma DPH levels of more than 10 mug/ml were achieved within 16 to 38 hr in the children given loading doses and within 5 days in the conventionally dosed children. No immediate side effects were noted, but within 8 to 10 days 9 of 13 children developed a generalized skin rash. Plasma p-OH-DPH (free or conjugated) paralleled DPH during the accumulation phase but not during DPH elimination. The ratio of metabolite to DPH in plasma showed both an interindividual variation and an inverse relation to the level of DPH. Identical twins in the study had a similar ratio and plasma level-time course profile. It is concluded that the loading dose regiment achieves an appropriate plasma level of DPH rapidly, that saturation kinetics are operative for p-OH-DPH formation, that the ratio of metabolite to DPH in plasma is an individual characteristic in children, and that further studies on the delayed toxicity are needed before the loading dose regimen can be recommended.
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