A comparison of phenytoin-loading techniques in the emergency department.

OBJECTIVES: To compare the effectivenesses of three phenytoin-loading techniques. METHODS: Patients with subtherapeutic phenytoin concentrations who presented within 48 hours of a seizure were randomized to receive either 20 mg/kg of oral phenytoin (PO), divided in maximum doses of 400 mg every two hours, 18 mg/kg of intravenous phenytoin (IVP) at an initial infusion rate of 50 mg/min, or 18 mg/kg (phenytoin equivalents) of intravenous fosphenytoin (IVF) at an initial infusion rate of 150 mg/min. RESULTS: A total of 45 patients were enrolled: 16 in the PO group, 14 in the IVP group, and 15 in the IVF group. The times required to reach therapeutic drug concentrations were (mean +/- standard deviation [SD]) 5.62 +/- 0.28 hours, 0.24 +/- 0.3 hours, and 0.21 +/- 0.28 hours, respectively. A total of 17, 27, and 32 adverse drug events were observed in the PO, IVP, and IVF groups, respectively, with significantly fewer events in the PO group (p = 0.02, p = 0.01). No significant difference was found between the numbers of necessary adjustments to the infusions in the two IV groups. The average time to safe emergency department discharge was significantly shorter for the IV groups compared with the PO group (p < 0.001). CONCLUSIONS: Oral loading has fewer adverse drug events than either IV loading method, but its use may be limited when therapeutic concentrations are required quickly. Although IVF loading is faster, from an adverse-drug event perspective, no advantage of IVF over IVP was apparent.

An NMR investigation of the conformational equilibria of 2-(2'-pyridyl)ethylphosphonic acid in several solvents.

Vicinal proton-proton NMR couplings have been used to investigate whether the position of conformational equilibria is determined by intramolecular N-H hydrogen bonding for 2-(2'-pyridyl)ethylphosphonic acid 1 in its various possible ionization states in water, methanol, ethanol, and dimethyl sulfoxide (DMSO). With 1 in the form of its monoanion and dianion, the trans is favored, with the dianion being more trans than the monoanion for a given solvent, probably as the result of steric effects, possibly enhanced by repulsive electrostatic effects between the negatively charged phosphonic group and the lone pair on the pyridine nitrogen. For 1 and its conjugate acid, the gauche amounts, respectively, to 43% and 45% in water, 66% and 51% in methanol, 66% and 64% in ethanol, and 29% and 49% in DMSO. For these latter two species, electrostatic, steric, and hydrogen bonding-effects are all likely to play a role in determining the conformational equilibria.