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BMJ (Clinical Research Ed.) Nov 1992
Review
Topics: Dose-Response Relationship, Drug; Drug Monitoring; Humans; Phenytoin; Plasma; Time Factors
PubMed: 1467727
DOI: 10.1136/bmj.305.6863.1215 -
British Medical Journal Feb 1971
Topics: Chlordiazepoxide; Diazepam; Phenytoin
PubMed: 5541733
DOI: 10.1136/bmj.1.5744.346-a -
Turkish Neurosurgery 2011Cerebro-spinal fluid (CSF) leakage caused by defects on the dura mater after trauma or some neurosurgical interventions is an important issue. In this study, we...
AIM
Cerebro-spinal fluid (CSF) leakage caused by defects on the dura mater after trauma or some neurosurgical interventions is an important issue. In this study, we investigated the effects of local and systemic use of phenytoin sodium on dural healing.
MATERIAL AND METHODS
Thirty-six male Wistar rats were divided into control, local phenytoin and systemic phenytoin groups with 12 rats in each. For each group, a dura defect was created at thoracic segment. Subjects were sacrificed at following 1st and 6th weeks and damaged segments were isolated. The results were compared histopathologically by Hematoxylin-Eosin and Masson-Trichrome staining. Criteria for the rate of collagen, neovascularization, and granulation formation were assessed semi quantitatively according to the histological assessment scale modified by Ozisik et al.
RESULTS
Better healing was achieved in the systemic and local phenytoin groups than in the control group. The level of healing was significantly higher in the systemic group in both early and late periods than in other groups (p < 0.01). The level of healing in the late-local group was also statistically significantly higher than that in the control group.
CONCLUSION
We observed that both systemic and local uses of phenytoin sodium (especially systemic) have positive effects on dura healing.
Topics: Animals; Anticonvulsants; Cerebrospinal Fluid Leak; Cerebrospinal Fluid Rhinorrhea; Disease Models, Animal; Dura Mater; Granulation Tissue; Male; Neurosurgical Procedures; Phenytoin; Rats; Rats, Wistar; Wound Healing
PubMed: 22194102
DOI: No ID Found -
British Journal of Clinical Pharmacology Apr 19771 Concentrations of phenytoin in mixed, parotid and submandibular saliva and serum were determined in normal subjects after an oral dose, using a specific double...
1 Concentrations of phenytoin in mixed, parotid and submandibular saliva and serum were determined in normal subjects after an oral dose, using a specific double antibody radioimmunoassay which requires only 20 micronl fluid. 2 Semi-log concentration-time plots of phenytoin concentration in mixed saliva and serum gave good parallelism after the initial 14 h post-administration period. 3 The mean ratio of the mixed saliva: serum phenytoin concentration was 10.3% +/- 1.5 (s.d.) in seven normal subjects. 4 Phenytoin concentrations found in separate parotid and submandibular salivary fractions did not differ but were significantly greater (P less than 0.001) than those found in mixed saliva. 5 Phenytoin concentrations in all salivary fractions were independent of the volume of fluid produced and the degree of stimulation. 6 The rate of phenytoin secretion in the parotid and submandibular fluid was proportional to the salivary flow rate. 7 These data suggest that mixed saliva may be a suitable medium for the monitoring of phenytoin concentrations and may provide a non-invasive alternative to the direct determination of phenytoin in serum.
Topics: Adult; Humans; Male; Methods; Parotid Gland; Phenytoin; Radioimmunoassay; Saliva; Salivation; Submandibular Gland; Time Factors
PubMed: 861132
DOI: 10.1111/j.1365-2125.1977.tb00692.x -
British Journal of Clinical Pharmacology Dec 1976Serum total and free fraction of thyroxine and triiodothyronine and urinary losses of unconjugated hormones in normal subjects and in patients treated long-term with... (Clinical Trial)
Clinical Trial
Serum total and free fraction of thyroxine and triiodothyronine and urinary losses of unconjugated hormones in normal subjects and in patients treated long-term with therapeutic doses of phenytoin have been measured. Decreases in serum total hormone concentrations with increased free fractions and resultant significant increase in the concentration of free thyroxine but not triiodothyronine were apparent in phenytoin-treated subjects. However, serum free hormone concentrations remained within the euthyroid range. These changes in serum free hormone concentration were reflected by an increased urinary loss of unconjugated thyroxine, but normal excretion of unconjugated triiodothyronine. Phenytoin in therapeutic doses displaces thyroxine and to a lesser extent, triiodothyronine from binding proteins in serum and thus increases peripheral clearance of thyroid hormones.
Topics: Adult; Anticonvulsants; Female; Humans; Male; Middle Aged; Phenytoin; Thyroid Gland; Thyroid Hormones; Young Adult
PubMed: 22216527
DOI: 10.1111/j.1365-2125.1976.tb00355.x -
Drugs in R&D Mar 2020The aim of this study was to determine whether the current method of calculating a fosphenytoin reloading dose results in a therapeutic free phenytoin level on...
OBJECTIVE
The aim of this study was to determine whether the current method of calculating a fosphenytoin reloading dose results in a therapeutic free phenytoin level on subsequent days.
METHODS
Medical records of patients receiving fosphenytoin in the neurocritical care unit between July 2017 and June 2018 were screened. Included patients were those who had received at least three doses of fosphenytoin and required reloading doses according to concentrations obtained through therapeutic drug monitoring. Free phenytoin levels were categorized based on the prespecified patient-specific target range, generally between 1.5 and 2.5 mcg/mL.
RESULTS
Of the fosphenytoin reloading doses administered, 48% (73/152) resulted in a therapeutic free phenytoin concentration on the subsequent day, with the remaining 52% resulting in nontherapeutic levels (39% subtherapeutic, 13% supratherapeutic). Our evaluation of reloading dose calculation strategies indicated that patients were two times as likely to obtain a therapeutic level when a modified pharmacokinetic equation omitting the use of volume of distribution or salt formulation was used (58%, n = 39) than they were with doses calculated using the current pharmacokinetic model (41%, n = 20) or doses based on provider preference (39%, n = 14).
CONCLUSION
The current method of calculating a fosphenytoin reloading dose in the critically ill population does not consistently result in therapeutic concentrations. With multiple factors affecting the pharmacokinetics of critically ill patients, the creation of a new pharmacokinetic model with less emphasis on volume of distribution may more consistently result in therapeutic concentrations.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Injuries; Critical Care; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Intensive Care Units; Male; Middle Aged; Phenytoin; Retrospective Studies; Seizures; Young Adult
PubMed: 31925752
DOI: 10.1007/s40268-019-00292-1 -
Indian Journal of Pharmacology 2016Phenytoin is a commonly used antiepileptic medication in the pediatric age group, but it has a narrow therapeutic range. Various adverse effects have been reported...
Phenytoin is a commonly used antiepileptic medication in the pediatric age group, but it has a narrow therapeutic range. Various adverse effects have been reported commonly. We report a relatively rare case of encephalopathy in a child from overdose of injectable phenytoin due to ignorance of the previous treatment. Scrutiny of medical records and history is of utmost importance while administering such medications.
Topics: Anticonvulsants; Brain; Brain Diseases; Child; Drug Overdose; Humans; Magnetic Resonance Imaging; Male; Medication Errors; Phenytoin; Seizures; Treatment Outcome
PubMed: 27756964
DOI: 10.4103/0253-7613.186209 -
British Journal of Clinical Pharmacology Jul 1984The plasma protein binding of phenytoin was studied in nine epileptic patients before and during addition of sodium valproate to the drug therapy. The free phenytoin...
The plasma protein binding of phenytoin was studied in nine epileptic patients before and during addition of sodium valproate to the drug therapy. The free phenytoin fraction in plasma was significantly greater during sodium valproate treatment. The mean free fraction rose from 0.135 +/- 0.019 (s.d.) to 0.182 +/- 0.030. Total plasma phenytoin concentration fell significantly from a range of 4.3-26.2 micrograms/ml to 3.4-19.8 micrograms/ml during sodium valproate treatment. Neither the free plasma concentration nor the saliva concentration of phenytoin was significantly altered by sodium valproate. No significant correlation was found between plasma valproic acid concentrations and the change in phenytoin binding. We conclude that valproic acid displaces phenytoin from plasma protein binding sites but does not inhibit its metabolism.
Topics: Adult; Binding, Competitive; Epilepsy; Female; Humans; Male; Middle Aged; Phenytoin; Protein Binding; Saliva; Serum Albumin; Valproic Acid
PubMed: 6430316
DOI: 10.1111/j.1365-2125.1984.tb05015.x -
Scientific Reports Jul 2020Hemodialysis (HD) has limited efficacy towards treatment of drug toxicity due to strong drug-protein binding. In this work, we propose to infuse a competitor drug into...
Hemodialysis (HD) has limited efficacy towards treatment of drug toxicity due to strong drug-protein binding. In this work, we propose to infuse a competitor drug into the extracorporeal circuit that increases the free fraction of a toxic drug and thereby increases its dialytic removal. We used a mechanistic model to assess the removal of phenytoin and carbamazepine during HD with or without binding-competition. We simulated dialytic removal of (1) phenytoin, initial concentration 70 mg/L, using 2000 mg aspirin, (2) carbamazepine, initial concentration 35 mg/L, using 800 mg ibuprofen, in a 70 kg patient. The competitor drug was infused at constant rate. For phenytoin (~ 13% free at t = 0), HD brings the patient to therapeutic concentration in 460 min while aspirin infusion reduces that time to 330 min. For carbamazepine (~ 27% free at t = 0), the ibuprofen infusion reduces the HD time to reach therapeutic concentration from 265 to 220 min. Competitor drugs with longer half-life further reduce the HD time. Binding-competition during HD is a potential treatment for drug toxicities for which current recommendations exclude HD due to strong drug-protein binding. We show clinically meaningful reductions in the treatment time necessary to achieve non-toxic concentrations in patients poisoned with these two prescription drugs.
Topics: Aspirin; Binding, Competitive; Carbamazepine; Humans; Ibuprofen; Models, Chemical; Phenytoin; Protein Binding; Renal Dialysis
PubMed: 32647294
DOI: 10.1038/s41598-020-68333-3 -
Kidney International May 1988In this study, changes of protein binding of nine drugs were evaluated. In addition, theophylline and phenytoin, the two drugs with the most substantial and progressive...
In this study, changes of protein binding of nine drugs were evaluated. In addition, theophylline and phenytoin, the two drugs with the most substantial and progressive decrease in protein binding, were further studied by high performance liquid chromatography (HPLC)-fractions of ultrafiltrate of normal and uremic serum, in an attempt to identify substances causing drug protein binding inhibition. There was a marked decline of the protein binding of theophylline, phenytoin and methotrexate (dialyzed patients vs. normals: -20.1, -16.0 and -15.1%, respectively). There was a rise in the protein binding of propranolol, cimetidine and clonidine. The changes observed for diazepam, prazosin and imipramine were less marked. For phenytoin, theophylline, methotrexate and diazepam, protein binding was inversely correlated to the serum creatinine (r = 0.87, 0.80, 0.79 and 0.67, P less than 0.001), and a less pronounced but still significant positive correlation was found for clonidine (r = 0.46, P less than 0.01). Ultrafiltrate, obtained during a hemofiltration session, inhibited protein binding of theophylline and phenytoin in a dose dependent way. After separation of this ultrafiltrate by HPLC, it appeared that for both theophylline and phenytoin at least a part of this inhibitory activity corresponded to the elution zone of hippuric acid. For theophylline two other inhibitory zones were further recognized: one corresponding to the elution zone of NaCl and one in which the responsible substance remained unidentified. Hippuric acid in solution inhibited protein binding of theophylline and phenytoin in a dose dependent way. In conclusion, protein binding of several drugs currently used in renal failure is affected in parallel with renal function, which might affect the therapeutic effectiveness of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Blood Proteins; Chromatography, High Pressure Liquid; Humans; Kidney Failure, Chronic; Pharmaceutical Preparations; Phenytoin; Protein Binding; Sodium Chloride; Theophylline; Ultrafiltration; Uremia
PubMed: 3392889
DOI: 10.1038/ki.1988.99