Phenytoin is a weak acid with a pKa of 8.3. Thus, in the acid milieu of the stomach, and even at physiologic pH, its aqueous solubility is limited. The parenteral form of phenytoin is adjusted to pH 12 to keep the drug in solution, but it is very irritating to the tissues, and intramuscular injections result in local precipitation of phenytoin with erratic absorption and is, therefore, not recommended. Absorption after oral ingestion is slow, variable, and often incomplete, especially following an overdose. Consequently, it is necessary to obtain serial levels in suspected overdose, to determine peak levels. Significant differences in bioavailability exist among different phenytoin preparations. Peak levels typically occur anywhere from 3 to 12 h after a single oral dose.

Following absorption, phenytoin is distributed throughout the body with a volume of distribution of 0.6 L/kg. Brain tissue concentrations equal those in plasma within about 10 min of intravenous infusion and correlate with therapeutic effects, whereas cerebrospinal fluid and myocardium equilibrate within 30 to 60 min. At steady state, concentrations are higher in neural tissue than in the serum. Within the CNS, concentrations are higher in the brainstem and cerebellum than in the cerebral cortex.

Dealing With Back Pain

Dealing With Back Pain

Deal With Your Pain, Lead A Wonderful Life An Live Like A 'Normal' Person. Before I really start telling you anything about me or finding out anything about you, I want you to know that I sympathize with you. Not only is it one of the most painful experiences to have backpain. Not only is it the number one excuse for employees not coming into work. But perhaps just as significantly, it is something that I suffered from for years.

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