RESUMO
Arabogalactane sulphate of quinidine (AGSQ) is a slow release preparation of quinidine. The aim of this study was to compare the plasma levels of quinidine obtained by different preparations of AGSQ (AGSQ I, II and III) and to determine which was best suited to therapeutics. The "in vitro" study showed different amounts of quinidine liberated in 6 hours, 34% with AGSQ I, 58% with AGSQ II and 100% with AGSQ III. The plasma quinidine levels were studied after administration of a dose corresponding to 330 mg quinidine base, morning and evening for 7 consecutive days to 27 hospitalised patients; 7 received AGSQ I, 11 received AGSQ II 5, received AGSQ III and 4 quinidine sulphate. The delay in reaching a steady state was 24 hours for the quinidine sulphate 36 hours for AGSQ I, 48 hours for AGSQ II and 60 hours for AGSQ III. The average plasma level on the 7th day (Cee) was 2.74 +/- 0.71 microgram/ml, 2.62 +/- 0.74 microgram/ml and 3.29 +/- 0.72 microgram/ml respectively. The plasma quinidine levels were maintained between toxic and therapeutic levels (3,5 and 1,7 microgram/ml) only with AGSQ II by suppressing the peak observed 1 hour administration of quinidine sulphate. An excellent correlation (r = 0,984) was observed between the plasma quinidine 6 hours after ingestion and the Cee. A blood test during the steady state, 6 hours after ingestion of the drug, is useful in adjusting the dosage. These results suggest that AGSQ II is the preparation best suited for therapeutic usage although it does not give the best relative bioavailability of the drug.
Assuntos
Quinidina/sangue , Preparações de Ação Retardada , Humanos , Cinética , Quinidina/administração & dosagem , Quinidina/uso terapêutico , SolubilidadeRESUMO
BACKGROUND: Secondary prevention is a key strategy for reducing levels of coronary heart disease, but a gap between guidelines and practice remains. OBJECTIVES: The aim of this double-part survey was to evaluate the improvement in secondary prevention one year after acute coronary syndrome (ACS) in real life, between 1999 and 2005, with respect to the change in guidelines. METHODS: Two surveys of almost similar design were performed in 1999 and 2005-2006. In each survey, unselected consecutive patients suffering from ACS (n=112 hospitalized in 1998, and n=110 in 2004) were evaluated at admission, and one year after hospitalization, for the risk factors, lifestyle, and achievement of therapeutic goals recommended by the most recent guidelines. Follow-up (FU) data were obtained by mail and phone contact with patient, general practitioner and cardiologist, and medical laboratory when appropriate. RESULTS: At 1-year FU (n=192 survivors with FU), smoking cessation (87% in 1999 versus 89% in 2005) and obesity (13% versus 19%, respectively) did not vary significantly. Blood pressure was controlled (< 140/90 mmHg, excepted in diabetics in 2005 with less than 130/80 mmHg) in 65% versus 80% (p<0.03). The rate of patients with no or controlled diabetes mellitus decreased from 1999 to 2005 (90% versus 76%), despite more intensive treatment (insulin in 1% versus 20%).The goals for LDL cholesterol were achieved in 47% of patients in 1999 (< 3.4 mmol/L) and in 76% in 2005 (< 2.6 mmol/L) (p<0.0001). Goals for triglycerides were achieved in 86% in 1999 (< 2g/L), and in 80% in 2005 (< 1.5 g/L) (NS). Besides, 63% of patients received an hypolipemic drug in 1999 (a statin in 59%) and 91% in 2005 (a statin in 88%). Mean number of controlled risk factors was 3.96+/-1.52 in 1999 versus 4.94+/-1.83 in 2005, and prevalence of pts with more than five controlled risk factors at one year FU increased from 15 to 44% (p<0.0001). CONCLUSIONS: These results, drawn from unselected consecutive patients managed in real life, demonstrate an improvement in secondary prevention one year after ACS, between 1999 and 2005, despite strengthened guidelines for blood pressure, triglycerides and LDL cholesterol levels. Control of obesity and diabetes remains unoptimal.