Phenytoin peak-plasma levels

Phenytoin may be administered either orally or intravenously and is absorbed slowly after oral administration, with peak plasma levels achieved after 3 to 12 hours. It is extensively plasma protein bound ( 90%), and the elimination half-life is between 15 and 30 hours. These large ranges reflect the considerable variability observed from patient to patient. Parenteral administration of phenytoin is usually limited to the intravenous route. Phenytoin for injection is dissolved in a highly alkaline vehicle (pFI 12). This alkaline vehicle is required because phenytoin is weakly acidic and has very poor solubility in its un-ionized form. Reportedly, however, its phosphate ester fosphenytoin has water solubility advantages over phenytoin for injection. Intramuscular phenytoin generally is avoided, because it results in tissue necrosis at the site of injection and erratic absorption because of high alkalinity. In addition, intermittent intravenous infusion is required to reduce the incidence of severe phlebitis. 

In one study, 32 patients with intraparenehymatous neurocysticercosis were given albendazole 7.5 mg/kg every 12 hours for 8 days. These patients were also taking either phenytoin 200 to 300 mg daily (9 patients), carbamazepine 600 to 1200 mg daily (9 patients), or phenobarbital 100 to 300 mg daily (5 patients) all for at least 3 months, and a eontrol group consisting of 9 patients who did not receive any antiepilepties. The AUCs for (+)-albendazole sulfoxide were 66%, 49%, and 61% lower than the control group for the phenytoin, carbamazepine, and phenobarbital groups respectively. The maximum plasma levels of (+)-albendazole sulfoxide were 50 to 63% lower and the half lives about 3 to 4 hours shorter. The AUCs, peak plasma levels and half-life of (-)-albendazole sulfoxide (present in much lower levels than the (+)-isomer) were similarly reduced by the antiepileptics. ... 

Single doses of carbamazepine 200 mg, phenobarbital 120 mg or phenytoin 200 mg were given to 3 groups of 6 healthy subjects with and without a single 600-mg dose of quinine sulfate. The AUC of carbamazepine and phenobarbital were increased by 104% and 57%, respectively, and the peak plasma levels were increased by 81% and 53%, respectively. Phenytoin was not significantly affected. The reasons for these effects are not known but the authors suggest that quinine inhibits the metabolism of carbamazepine and phenobarbital (but not phenytoin) by the liver, so that their levels become raised. ... 

Phenytoin s absorption is slow and variable yet almost complete absorption eventually occurs after po dosing. More than 90% of the dmg is bound to plasma protein. Peak plasma concentrations are achieved in 1.5—3 h. Therapeutic plasma concentrations are 10—20 lg/mL but using fixed po doses, steady-state levels are achieved in 7—10 days. Phenytoin is metabolized in the fiver to inactive metabolites. The plasma half-life is approximately 22 h. Phenytoin is excreted primarily in the urine as inactive metabolites and <5% as unchanged dmg. It is also eliminated in the feces and in breast milk (1,2). Prolonged po use of phenytoin may result in hirsutism, gingival hyperplasia, and hypersensitivity reactions evidenced by skin rashes, blood dyscrasias, etc... 

After an oral dose of the sodium salt, peak plasma phenytoin levels occur from one (H5) to between 4 and 8 hours (D5) later. After either oral or intravenous administration, phenytoin accumulates rapidly in organs such as the liver, kidney, and salivary glands, and maximum levels are reached within 30 minutes even in tissues such as the brain and skeletal muscle, which accumulate phenytoin more slowly. Uptake by fat is delayed (N5). 

After taking felodipine 10 mg daily for 4 days, 10 epileptics (ineluding 4 taking carbamazepine alone and 3 taking carbamazepine with phenytoin) had markedly reduced plasma felodipine levels (peak levels of 1.6 nanomol/L compared with 8.9 nanomol/L in 12 control subjects). The felodipine bioavailability was reduced to 6.6%. A study in 8 subjects found that the AUC of felodipine was reduced by only 28% by oxcar-bazepine 600 to 900 mg daily for a week. ... 

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