Bioequivalencia y farmacodinamia de 2 formulaciones de quinidina de liberación prolongada en perros / Bioequivalence and pharmacodynamics of 2 sustained-release quinidine formulations in dogs

Se comprobó la bioequivalencia y los efectos farmacodinámicos de 2 formulaciones de quinidina, tabletas de liberación prolongada desarrollada en el CIDEM (IMEFA, Cuba). Ambas contenían 166 mg de la sustancia biológicamente activa en forma de base. En el estudio se utilizaron perros beagles (n=6), siguiendo un diseño aleatorio cruzado. No se detectaron diferencias significativas entre las concentraciones máximas, el tiempo al que se alcanza la concentración máxima y las áreas bajo la curva, lo cual permite plantear que ambas formulaciones desde el punto de vista farmacocinético son bioequivalentes

Comparación farmacocinética de 2 formulaciones de quinidina en voluntarios sanos / Comparison of pharmacokinetics of 2 quinidine formulations in healthy volunteers

Se realizó un estudio comparativo del curso temporal de las concentraciones plasmáticas de quinidina en voluntarios sanos, y se determinaron los parámetros farmacocinéticos fundamentales en tabletas convencionales de quinidina sulfato y tabletas de liberación prolongada elaboradas a partir de un complejo polimetacrilato-quinidina. Se concluyó que resultó adecuado al régimen de dosificación de 2 tabletas de quinidina de liberación prolongada cada 12 horas para lograr un perfil de concentración plasmática vs. tiempo, característico de este tipo de formulación, con el valor de tiempo de vida media de eliminación de 12,8 horas en comparación con 4,5 horas que presentó la tableta convencional de sulfato de quinidina

Determination of quinine and quinidine in biological fluids by high performance liquid chromatography.

A simple, specific, rapid and sensitive High Performance Liquid Chromatography (HPLC) method has been developed to measure plasma level of quinine and quinidine. The drugs were extracted successively from plasma at basic pH with chloroform and quantified on a revers-phase Z-module C18 HPLC column with fluorescence detector (excitation 340 nm, emission 425 nm). The isocratic mobile phase used was the mixture of 0.05 M ammonium formate and acetonitrile (93.5:6.5, v/v), adjusted pH to 2.0 with ortho-phosphoric acid. The limits of quantitation for these compounds were as low as 4 ng/ml of plasma, using a 0.25 ml specimen. Calibration curves were linear (R squared = 0.9994) in the range 0-7,000 ng/ml. An interassay reproducibility was 6.8%, 0.3% and 1.2% at the concentrations of 250 ng, 4,000 ng and 8,000 ng of quinine, respectively. Inter-assay coefficient of variation of quinidine was 1.8%, 2.7% and 3.7% at the concentrations of 250 ng, 1,500 ng and 3,000 ng, respectively. Recovery of quinine and quinidine were 76% and 81%, respectively. The method has been used in the analysis of quinine and quinidine in healthy volunteers receiving quinine or quinidine intravenously. The method is now being used to assay samples from field studies with satisfactory results.

Polarisation fluoroimmunoassay for quinine in serum and urine.

The development and validation of a polarisation fluoroimmunoassay for the antimalarial drug quinine is described. The assay is performed either by sequential addition of the reagents or by a single-reagent technique whereby the tracer and antibodies are premixed. Serum samples require pepsin digestion prior to assay while urine specimens are assayed directly. The reliability criteria of the assay are satisfactory and no cross-reaction is detected with quinidine (the optical isomer of quinine) or with common antimalarial drugs. The assay was applied to the measurement of quinine in urine specimens obtained from a single-dose pharmacokinetic study and the results correlated with those of the benzene extraction fluorescence method for quinine measurement.

Estudo com o sulfato de quinidina: correlaçöes clínicas com seus níveis plasmáticos / Quimidine sulfate: clinical correlation with its plasma levels

O presente estudo teve por objetivo avaliar a eficácia e a tolerância de um sal de quinidina, de açäo rápida, no tratamento de 40 pacientes portadores de diversas arritmias supraventriculares, em comparaçäo com o placebo administrado nos 10 primeiros dias dos 90 dias de observaçäo previstos no protocolo original. Após 7 dias de tratamento, a ao término do estudo, foram efetuadas as comparaçöes pelo método fluorimétrico de Udenfriend. O tratamento foi bem tolerado em todos os pacientes, apenas com discretos efeitos colaterais em 30%. Os resultados obtidos revelaram uma eficácia de cerca de 70% do sulfaro de quinidina na amostra estudada, sendo a concentraçäo plasmática média de 4,6 ñ 1,3, após 7 dias, e de 6,2 ñ 1,3, ao final do estudo, devido ao efeito cumulativo da substância. Os autores destacam a importância, na prática diária, da dosagem da quinidina plasmática, representando um método de baixo custo e de grande utilidade para evidenciar níveis elevados de droga no plasma, permitindo um manuseio fácil e mais seguro desta substância e evitando os fenômenos de intoxicaçäo dela decorrente, ao contrário dos outros antiarrítmicos comercialmente disponíveis