Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery
The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary art...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2005-05-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000500008 |
| _version_ | 1818701849824329728 |
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| author | M.J.C. Carmona L.M.S. Malbouisson V.A. Pereira M.A. Bertoline C.E.K. Omosako K.B. Le Bihan J.O.C. Auler Jr. S.R.C.J. Santos |
| author_facet | M.J.C. Carmona L.M.S. Malbouisson V.A. Pereira M.A. Bertoline C.E.K. Omosako K.B. Le Bihan J.O.C. Auler Jr. S.R.C.J. Santos |
| author_sort | M.J.C. Carmona |
| collection | DOAJ |
| description | The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m²), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9) to 10.6 h (95% CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3) to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6) vs 10.7 ml min-1 kg-1 (95% CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period. |
| first_indexed | 2024-12-17T15:27:23Z |
| format | Article |
| id | doaj.art-40ceccec7c114b99b8a8418addd474cf |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-12-17T15:27:23Z |
| publishDate | 2005-05-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-40ceccec7c114b99b8a8418addd474cf2022-12-21T21:43:14ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2005-05-0138571372110.1590/S0100-879X2005000500008Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgeryM.J.C. CarmonaL.M.S. MalbouissonV.A. PereiraM.A. BertolineC.E.K. OmosakoK.B. Le BihanJ.O.C. Auler Jr.S.R.C.J. SantosThe pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m²), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9) to 10.6 h (95% CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3) to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6) vs 10.7 ml min-1 kg-1 (95% CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000500008PropranololPharmacokineticsCardiopulmonary bypass |
| spellingShingle | M.J.C. Carmona L.M.S. Malbouisson V.A. Pereira M.A. Bertoline C.E.K. Omosako K.B. Le Bihan J.O.C. Auler Jr. S.R.C.J. Santos Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery Brazilian Journal of Medical and Biological Research Propranolol Pharmacokinetics Cardiopulmonary bypass |
| title | Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery |
| title_full | Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery |
| title_fullStr | Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery |
| title_full_unstemmed | Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery |
| title_short | Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery |
| title_sort | cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery |
| topic | Propranolol Pharmacokinetics Cardiopulmonary bypass |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000500008 |
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