ABSTRACT
Objective. To determine individual digoxin level variations and the effect of some common diseases those aggravate congestive heart failure (CHF) on digoxin pharmacokinetics in children. Design. Digoxin pharmacokinetics was evaluated in 11 children with CHF and an additional disease, such as rheumatic fever, anemia or infections. Digoxin plasma levels were monitored in patients on multiple-dose regime. Setting. Third level pediatric hospital. Results. Pharmacokinetic parameters showed extensive variation; median values were: elimination half-life 42.0 hrs (8.3-77.0), volume of distribution 1.01 L/kg (0.654-6.25), and clearance 15.0 mL/kg/h (6.0-331.8), which differed from results in patients with only CHF, reported previously. Dosage schemes in use at the Cardiology Service produced the following results: 40.5% of patients reached therapeutic levels, 10.8% toxic levels and 48.6% sub-therapeutic levels. Conclusion. The range of dosage required in order to adjust individual treatments was very wide, leading us to the conclusion that therapeutic schemes for this population should be individualized based on their pharmacokinetic parameters, and therapeutic monitoring of drugs should be performed.
El objetivo del presente estudio es determinar el efecto de algunas enfermedades que agravan la insuficiencia cardiaca congestiva (ICC) sobre la farmacocinètica de digoxina en niños. Diseño. Se estudió la farmacocinètica de digoxina en 11 niños con ICC, agravada por otras enfermedades como fiebre reumática, anemia o infecciones. Posteriormente se llevó a cabo monitoreo de los niveles de digoxina mientras seguían un règimen de dosis múltiple. Lugar. Centro de atención de tercer nivel. Resultados. Los parámetros farmacocinèticos mostraron amplia variabilidad: los valores de las medianas fueron: vida media de eliminación 42.0 horas (8.3-77.0), volumen de distribución 1.01 L/kg (0.654-6.25), y depuración 15.0 mL/kg/h (6.0-331.8) los cuales son diferentes a los de los pacientes que únicamente padecen ICC previamente reportados. Con el esquema de dosis usado en el Servicio de Cardiología se encontraron los siguientes resultados: 40.5% de las muestras de pacientes alcanzaron niveles terapèuticos, 10.8% niveles tóxicos y 48.6% subterapèuticos. Conclusión. Debido a la variación en los parámetros farmacocinèticos individuales, ocasionados por las patologías que agravan la ICC, se recomienda individualizar los esquemas de dosificación a partir de criterios farmacocinèticos, sin prescindir del monitoreo terapèutico del fármaco.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Cardiotonic Agents/pharmacokinetics , Digoxin/pharmacokinetics , Heart Failure/blood , Heart Failure/complications , Severity of Illness IndexABSTRACT
Background: The different therapeutic schedules used for the prescription of digoxin have little theoretical support. Aim: To measure digoxin plasma levels in patients using four different prescription schedules. Patients and methods: Four groups of patients were studied. Group I corresponded to 56 patients taking digoxin 0.25 mg/day, from Monday to Friday. Group II corresponded to 30 patients taking digoxin 0.25 mg/day, from Monday to Saturday. Group III corresponded to 53 patients taking digoxin 0.25 mg/day continuosly. Group IV corresponded to 36 patients taking digoxin 0.125 mg/day continuosly. Plasma digoxin levels were measured in two consecutive Mondays before taking the daily dose of the drug. Serum creatinine was also measured and creatinine clearance was calculated. The therapeutic plasma concentration range was set between 0.5 and 2 ng/ml. Results: Mean plasma digoxin levels were 1.15±0.8 ng/ml in group I, 1.4±0.55 ng/ml in group II, 1.68±0.7 ng/ml in group III and 1.14±0.43 ng/ml in group IV. 93 percent of patients in group I, 80 percent of patients in group I, 80 percent of patients in group II, 75 percent of patients in group III and 94 percent of patients in group IV had therapeutic digoxin levels. A low creatinine clearance, an age over 65 and interactions with other drugs were risk factors associated with supratherapeutic levels, mostly seen in group II and group III with 20 percent and 24 percent respectively. Conclusions: Most patients using digoxin with different therapeutic schedules had plasma drug levels within the therapeutic range
Subject(s)
Humans , Male , Female , Middle Aged , Digoxin , Atrial Fibrillation/drug therapy , Digoxin , Drug Interactions , Amiodarone , Hospitals, State , Cardiotonic Agents/pharmacokinetics , Cardiotonic Agents/bloodSubject(s)
Humans , Cardiotonic Agents/pharmacokinetics , Cyclic AMP/biosynthesis , Amrinone/pharmacokinetics , Calcium Channels/pharmacokinetics , Digitalis Glycosides/pharmacokinetics , Ventricular Dysfunction/drug therapy , Dobutamine/pharmacokinetics , Enoximone/pharmacokinetics , Cardiotonic Agents/classification , Dopamine/pharmacokinetics , Cyclic GMP/biosynthesis , Intraoperative CareABSTRACT
Como conseqüência do uso freqüente de medicaçäo simultânea podem advir tanto complicaçöes leves quanto reaçöes colaterais sérias e até fatais. A farmacologia tem progredido no sentido de permitir um melhor conhecimento da interaçäo das drogas, prevenindo a maioria destes efeitos adversos. Entretanto, a prevençäo é limitada, tendo em vista a discrepância entre o número de interaçöes publicadas e o número de possíveis combinaçöes de medicamentos em doentes