RESUMEN
1 Unexpectedly low plasma concentrations of mexiletine were observed in three patients treated with mexiletine and concurrently taking phenytoin. 2 Six healthy volunteers were given a single oral dose of mexiletine (400 mg), before and after 1 week of phenytoin administration (300 mg/day). 3 The mean +/- s.d. area under the plasma mexiletine concentration-time curve decreased from 17.67 +/- 6.21 to 8.01 +/- 3.64 micrograms ml-1 h (P less than 0.003). 4 The mean +/- s.d. half-life of elimination of mexiletine decreased from 17.2 +/- 5.26 to 8.4 +/- 4.17 h (P less than 0.02) 5 The suggested mechanism of the interaction is hepatic mixed-function oxidase enzyme induction by phenytoin. 6 The interaction is likely to be clinically significant.
Asunto(s)
Mexiletine/metabolismo , Fenitoína/farmacología , Propilaminas/metabolismo , Adulto , Disponibilidad Biológica , Interacciones Farmacológicas , Femenino , Humanos , Cinética , MasculinoRESUMEN
Large doses (up to 1200 mg) of phenytoin were required to achieve therapeutic plasma concentrations and to control post-traumatic seizures in a 62-year-old woman. The elimination half-life of phenytoin was calculated to be 3.5 hours. Frequent monitoring of the plasma concentration was essential to optimize the therapeutic control and to avoid systemic toxicity.
Asunto(s)
Epilepsia Postraumática/tratamiento farmacológico , Fenitoína/administración & dosificación , Resistencia a Medicamentos , Epilepsia Postraumática/metabolismo , Femenino , Humanos , Hígado/metabolismo , Persona de Mediana Edad , Fenitoína/metabolismo , Fenitoína/uso terapéuticoRESUMEN
A case of urinary crystalluria occurring in a patient during treatment with flucytosine (5-fluorocytosine) is presented. A reduction in the dosage of the 5-fluorocytosine resulted in a marked decrease in the excretion of urinary gravel which was shown to be a coprecipitate of 5-fluorocytosine and uric acid.
Asunto(s)
Criptococosis/orina , Citosina/análogos & derivados , Flucitosina/uso terapéutico , Flucitosina/orina , Enfermedades Pulmonares Fúngicas/orina , Ácido Úrico/orina , Criptococosis/tratamiento farmacológico , Cristalización , Humanos , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
A case of chlorbutol toxicity and dependence is presented. A very long elimination half-life (13.2 days) was found in the patient. The data suggest that chlorbutol is an unsuitable sedative to be available freely to the public.
Asunto(s)
Clorobutanol/efectos adversos , Trastornos Relacionados con Sustancias , Adulto , Clorobutanol/metabolismo , Humanos , MasculinoRESUMEN
A 49-year-old female with chronic alcoholism and epilepsy, treated with phenytoin, began to convulse when treatment with disulfiram (an inhibitor of phenytoin metabolism) was discontinued. The patient at this stage was resistant to the large doses of phenytoin, apparently owing to induction of the metabolism of this drug by chronic alcohol intake. Later, a small (30%) increase in dose resulted in about a tenfold increase in plasma concentration of phenytoin and severe toxicity. The final dose of phenytoin required to maintain the plasma level within the therapeutic range suggested that the enzyme induction had decreased. The value of monitoring plasma concentrations of phenytoin is emphasized.