RESUMEN
The antiarrhythmic agent encainide undergoes extensive first-pass hepatic metabolism after oral dosing. The active metabolites O-desmethylencainide and 3-methoxy-O-desmethylencainide are formed in subjects who are extensive metabolizers (EMs), a phenotypic trait that cosegregates with that of debrisoquin. Because of the possibility that drug metabolism is altered by liver dysfunction, the disposition of encainide and its metabolites was studied in six such EMs with cirrhosis and compared with that in eight normal subjects of the same phenotype. Patients with cirrhosis had lower systemic and oral clearances of encainide, resulting in a threefold increase in oral bioavailability. The plasma concentration of encainide was significantly higher among the patients with cirrhosis, whereas the plasma levels of the respective metabolites were comparable with those in normal subjects, resulting in no change in the patient's ECG intervals. Encainide is, therefore, an example of a drug in which cirrhosis causes a three- to fourfold increase in parent drug concentrations. However, because no change occurs in the levels of the pharmacologically active metabolites, dosage adjustment is probably not required in patients with cirrhosis.
Asunto(s)
Anilidas/metabolismo , Cirrosis Hepática/metabolismo , Administración Oral , Adulto , Anilidas/uso terapéutico , Disponibilidad Biológica , Encainida , Humanos , Infusiones Parenterales , Cinética , Cirrosis Hepática/tratamiento farmacológico , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , FenotipoRESUMEN
The pleuropulmonary complications of pancreatitis are protean. The subject of pancreatic pleural effusions has received avid attention in the recent literature with the demonstration of pancreaticopleural fistulization by endoscopic retrograde cholangiopancreatography. Surgical intervention has been efficacious when nonoperative management has failed. We report the successful nonoperative management of a case of alcohol-related pancreatitis complicated by bilateral pleural effusions, and then review the literature.