Phenytoin: Basic and clinical pharmacology

Jones, Gary L.; Wimbish, Gary H.; McIntosh, William E.

doi:10.1002/med.2610030403

Cited by 43 publications

(30 citation statements)

References 181 publications

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“…Phenytoin has very complex pharmacokinetics displaying saturable absorption, saturable metabolism (Michaelis-Menton kinetics), and high protein binding [23]. This drug is eliminated primarily by hepatic metabolism.…”

Section: Clinical Pharmacology Of Aedsmentioning

confidence: 99%

Transitional Polytherapy: Tricks of the Trade for Monotherapy to Monotherapy AED Conversions

Garnett

Louis

Henry

et al. 2009

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The goal of epilepsy therapy is to help patients achieve seizure freedom without adverse effects. While monotherapy is preferable in epilepsy treatment, many patients fail a first drug due to lack of efficacy or failure to tolerate an initial medication, necessitating an alteration in therapy. Sudden changes between monotherapies are rarely feasible and sometimes deleterious given potential hazards of acute seizure exacerbation or intolerable adverse effects. The preferred method for converting between monotherapies is transitional polytherapy, a process involving initiation of a new antiepileptic drug (AED) and adjusting it toward a target dose while maintaining or reducing the dose of the baseline medication. A fixed-dose titration strategy of maintaining the baseline drug dose while titrating the new medication is preferable when breakthrough seizures are occurring and no adverse effects are present. However, a flexible titration strategy involving reduction of the baseline drug dose to ensure adequate tolerability of the new adjunctive medication is preferred when patients are already experiencing adverse effects. This article reviews pharmacokinetic considerations pertinent for ensuring successful transitional polytherapy with the standard and newer antiepileptic drugs. Practical consensus recommendations “from an expect panel (SPECTRA, Study by a Panel of Experts Considerations for Therapy Replacement and Antiepileptics) for a successful monotherapy” AED conversions are then summarized. Transitional polytherapy is most successful when clinicians appropriately manage the titration strategy and consider pharmacokinetic factors germane to the baseline and new adjunctive medication.

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Section: Clinical Pharmacology Of Aedsmentioning

confidence: 99%

Transitional Polytherapy: Tricks of the Trade for Monotherapy to Monotherapy AED Conversions

Garnett

Louis

Henry

et al. 2009

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“…Aconitine is currently commercially available in various pharmaceutical forms, such as injections, capsules, etc. However, poor solubility in water (approximately 20 mg/ml) 5) and in physiologically acceptable organic solvents and instability problems induced by hydrolysis 6) present serious obstacles in the formulation of aconitine. Aconitine injection, which is extensively applied in treating advanced carcinomatous pain clinically, was reported to have many disadvantages such as serious adverse eŠects, short storage time due to instability, and patient low compliance caused by the need for high-frequency administration.…”

Section: Introductionmentioning

confidence: 99%

Crystalline Drug Aconitine-loaded Poly(d,l-Lactide-CoGlycolide) Nanoparticles: Preparation and <i>in Vitro</i> Release

Xiang

et al. 2010

YAKUGAKU ZASSHI

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This paper reports both the optimization of aconitine entrapment and its release from biodegradable poly(d,l-lactide-coglycolide) (PLGA) nanoparticles prepared using the O/W single-emulsion/solvent-evaporation technique. The in‰uence of several parameters, such as the initial aconitine mass, aqueous-phase pH, volume ratio of aqueous/organic phase (W/O), PLGA concentration in the organic phase, etc., on aconitine encapsulation were investigated. The optimized nanoparticles had an entrapment e‹ciency of 88.40±3.02％ with drug loading capacity of 9.42±2.93％. Crystallization growth, which played a crucial role in hindering the incorporation of aconitine into the polymer carrier, was proposed. DiŠerential scanning calorimetry and X-ray powder diŠraction demonstrated that aconitine existed in an amorphous state or as a solid solution in the polymeric matrix. The in vitro release proˆles exhibited a sustained release of aconitine from nanoparticles and a pH-dependent character in phosphate-buŠered saline with diŠerent pH values. Moreover, aconitine-loaded PLGA nanoparticles could lead to improvement in the stability of aconitine. This work demonstrated the feasibility of encapsulating aconitine into PLGA nanoparticles using the O/W single-emulsion/solvent-evaporation technique.

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“…Lamotrigine causes ataxia in marmosets at least five times the expected anticonvulsant dose (50 mg kg-'). In man phenytoin causes ataxia and nystagmus at plasma concentrations over 20,ug ml-', which can be easily demonstrated clinically (Jones et al, 1983). However not much is known about the effects of phenytoin on coordination and eye movements at therapeutic levels.…”

mentioning

confidence: 99%

“…The absorption of phenytoin is dose related (Jones et al, 1983) and this makes it difficult to attain therapeutic plasma levels in normal volunteers after single dose administration which for practical reasons is desirable. Several studies have been published in which effects of phenytoin in normal volunteers were measured using different dosage schedules and test methods (Haward, 1983;Houghton etal., 1973;Idestrom et al, 1973;Booker et al, 1967;Stephens et al, 1967).…”

mentioning

confidence: 99%

Lamotrigine (BW430C), a potential anticonvulsant. Effects on the central nervous system in comparison with phenytoin and diazepam.

Cohen¹,

Ashby²,

Crowley³

et al. 1985

Brit J Clinical Pharma

133

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1 Twelve healthy male volunteers received phenytoin 0.5 and 1 g, lamotrigine (a new anticonvulsant) 120 and 240 mg, diazepam 10 mg and placebo orally in a double-blind, cross-over, randomized trial.2 Maximum drug concentrations at 4 h, measured in plasma were 11.5 + 2.2 ,ug ml-' for phenytoin and 2.7 + 0.4 ,ug ml-' for lamotrigine. These levels were in the therapeutic range for phenytoin and the putative therapeutic range for lamotrigine.3 Side effects after diazepam (mainly sedation) and phenytoin (mainly unsteadiness) differed markedly from lamotrigine which produced no important side effects. Subjective effects as measured by visual analogue scales were caused by phenytoin and diazepam but not by lamotrigine. 4 Diazepam impaired eye movements, adaptive tracking and body sway. Phenytoin impaired adaptive tracking, increased body sway and impaired smooth pursuit eye movement. Lamotrigine produced only a possible slight increase in body sway. 5 There were significant correlations between performance and saliva levels of phenytoin and diazepam. 6 It was concluded that the tests used were suitable for monitoring CNS effects of anticonvulsants and that lamotrigine possibly could have a more favourable CNS side effect profile than phenytoin.

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Phenytoin: Basic and clinical pharmacology

Cited by 43 publications

References 181 publications

Transitional Polytherapy: Tricks of the Trade for Monotherapy to Monotherapy AED Conversions

Transitional Polytherapy: Tricks of the Trade for Monotherapy to Monotherapy AED Conversions

Crystalline Drug Aconitine-loaded Poly(d,l-Lactide-CoGlycolide) Nanoparticles: Preparation and <i>in Vitro</i> Release

Lamotrigine (BW430C), a potential anticonvulsant. Effects on the central nervous system in comparison with phenytoin and diazepam.

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