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      Obesity influences propranolol pharmacokinetics in patients undergoing coronary artery bypass grafting employing cardiopulmonary bypass Translated title: Influência da obesidade na farmacocinética do propranolol em pacientes submetidos à revascularização do miocárdio com circulação extracorpórea

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          Abstract

          Propranolol plasma levels and kinetic disposition may be altered by hypothermic cardiopulmonary bypass (CPB-H). We investigated the potential influence of obesity on propranolol pharmacokinetics in patients undergoing coronary artery bypass grafting employing CPB-H. Fifteen patients, receiving propranolol perorally pre- (10-40 mg, 2-3 times a day) and post-operatively (10 mg, once a day) were distributed in two groups, based on body mass index (BMI), in obese (n = 9, BMI: mean 29.4 kg/m²) and non-obese (n=6, BMI: mean 24.8 kg/m²). A serial of blood samples was collected at the pre- and post-operative periods at time dosing interval (Ä); propranolol plasma levels were measured one day before and after surgery using a high performance liquid chromatographic procedure described previously. PK Solutions software 2.0 was applied to obtain pharmacokinetic parameters. No changes on kinetic parameters as biological half-life (t1/2, p = 0.0625, NS), volume of distribution (Vd/F, p=0.8438, NS) and plasma clearance (CL T/F, p = 0.1563, NS) were obtained for the non-obese patients, while a prolongation of t1/2 (3.2 to 11.2 h, p< 0.0039), an increase on Vd/F (3.0 to 7.7 L/kg, p<0.0039) and reduction on CL T/F (11.3 to 9.2 mL/min.kg, p<0.0391) were obtained in the post-operative period for obese patients. Pharmacokinetic data could justify propranolol plasma concentrations in obese patients higher than in non-obeses, after surgery.

          Translated abstract

          As concentrações plasmáticas e a disposição cinética do propranolol podem ser alteradas pela circulação extracorpórea (CEC). Investigou-se a influência da obesidade na farmacocinética do propranolol em pacientes submetidos à revascularização do miocárdio empregando a CEC. Investigaram-se quinze pacientes, recebendo cronicamente propranolol no pré- (10-40 mg, 2 a 3 vezes ao dia PO) e no pós-operatório (10 mg, 1 vez ao dia) sendo os mesmos distribuídos em dois grupos: obesos (n = 9, média 29,4) kg/m²; e não-obesos (n = 6, média 24,8 kg/m²). Colheram-se amostras seriadas de sangue nos períodos pré- e pós-operatório (Ä); determinaram-se as concentrações plasmáticas do propranolol através da cromatografia líquida de alta eficiência. Aplicou-se o software PK Solutions 2.0 para estimativa dos parâmetros cinéticos. Não se registrou alteração na farmacocinética do propranolol avaliada através dos parâmetros meia-vida biológica (t1/2), volume de distribuição aparente (Vd/F) e depuração plasmática (CL T/F) no grupo de pacientes não-obesos, enquanto prolongamento relevante da t1/2 (3,2 para 11,2 h, p<0,0039), aumento no Vd/F (3,0 para 7,7 L/kg, p < 0,0039) e redução no CL T/F (11,3 para 9,2 mL/min.kg, p<0,0391) foram observados no grupo de pacientes obesos, no pós-operatório de revascularização do miocárdio empregando circulação extracorpórea e hipotermia. Os parâmetros farmacocinéticos obtidos poderiam justificar as concentrações plasmáticas do propranolol nos pacientes obesos superiores àquelas obtidas para não obesos após a cirurgia cardíaca.

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          Most cited references19

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          Liver in obesity.

          We report on clinical, nutritional, and hepatic histological findings in 50 non-selected obese subjects (mean overweight +74%; range +21-138%). The pathogenesis of the liver damage was assessed with the help of multidimensional analysis of a number of clinical variables. According to the severity of the hepatic lesions, the patients have been ranged in five groups: O (normal liver) 10%; I (fatty liver) 48%; II (fatty hepatitis) 26%; III (fatty fibrosis) 8%; IV (fatty cirrhosis) 8%. The more severe changes (groups III and IV) were constantly associated with excessive alcohol intake. The multidimensional analysis was unable to find a relationship between obesity and the development of fibrosis and cirrhosis whereas it showed that: (a) there was a highly significant correlation between the daily ethanol intake and the degree of overweight, (b) severe fatty metamorphosis was significantly associated with the degree of overweight, the existence of diabetes mellitus, and the amount of alcohol and fat intake, (c) nutritional factors, in particular deficient protein intake, have only an accessory effect in the development of mild inflammation and fibrosis, (d) the consumption of potentially hepatotoxic drugs, very high in the obese (about five drugs per day) could have a role in the development of cirrhosis. In conclusion in our study, there was no evidence that obesity per se could result in severe liver damage.
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            Vasodilatation and modulation of vasoconstriction in canine subcutaneous adipose tissue caused by activation of ²-adrenoceptors

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              Effect of cardiopulmonary bypass on the pharmacokinetics of drugs

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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                rbcf
                Revista Brasileira de Ciências Farmacêuticas
                Rev. Bras. Cienc. Farm.
                Divisão de Biblioteca e Documentação do Conjunto das Químicas da Universidade de São Paulo (São Paulo )
                1516-9332
                December 2003
                : 39
                : 4
                : 409-414
                Affiliations
                [1 ] Universidade de São Paulo Brazil
                [2 ] Universidade de São Paulo Brazil
                Article
                S1516-93322003000400008
                10.1590/S1516-93322003000400008
                3e8da5f8-0859-4fba-9c81-1ecc7d7c4dbe

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=1516-9332&lng=en
                Categories
                PHARMACOLOGY & PHARMACY

                Pharmacology & Pharmaceutical medicine
                Obesity,Propranolol,Pharmacokinetics,Hypothermic cardiopulmonary bypass,Farmacocinética,Circulação extracorpórea,Obesidade

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