Papaverine disposition in cardiac surgery patients and the effect of cardiopulmonary bypass

European Journal of Clinical Pharmacology - Tập 27 - Trang 127-130 - 1984
W. G. Kramer1,2, A. Romagnoli1,2
1Department of Pharmaceutics, University of Houston, Houston, USA
2Department of Cardiovascular Anesthesiology, Texas Heart Institute, Houston, USA

Tóm tắt

Cardiac surgery involving cardiopulmonary bypass (CPB) causes substantial physiologic changes which may potentially alter the pharmacokinetic properties of drugs used during and after the procedure. Studies with fentanyl have implied a relationship between prolonged elimination half-lives following CPB and decreased liver perfusion during and after the procedure. To further test this hypothesis, the effects of CPB on the pharmacokinetics of papaverine, a coronary vasodilator currently being added to the cardioplegic solution to prevent vasospasm, were studied. The drug was given to two groups of patients, one (n=6) undergoing surgery with and one (n=5) without CPB, the latter serving as controls. Plasma papaverine concentrations declined biexponentially in the control patients with a mean elimination half-life of 1.30±0.25 h, total plasma clearance of 13.8±3.75 ml/min/kg, volume of distribution of 1.52±0.45 l/kg and volume of distribution, steady-state, of 0.992±0.530 l/kg. For the CPB group, only half-life was estimated, and averaged 2.77±0.28 h, significantly greater (p<0.01) than that in the controls. These results further confirm the increased half-lives seen with other hepatically cleared drugs following CPB and have implications in the clinical management of patients given drugs eliminated in this manner.

Tài liệu tham khảo

Aaltonen L, Kanto J, Arola M, Iisola E, Pakkanen A (1982) Effect of age and cardiopulmonary bypass on the pharmacokinetics of lorazepam. Acta Pharmacol Toxicol 51: 126–131 Belpaire FM, Tosseel MT, Bogaert MG (1978) Metabolism of papaverine IV. Urinary elimination of papaverine metablites in man. Xenobiotica 178: 297–300 Brown PD, Manno JE (1978) Estrip, a Basic computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci 67: 1687–1697 Buxton AE, Goldberg S, Harker A, Hirshfeld J Jr, Kastor KA (1981) Coronary artery spasm immediately after myocardial revascularization. Recognition and management. New Eng J Med 304: 1249–1253 Garrett ER, Roseboom H, Green JR Jr, Schuermann W (1978) Pharmacokinetics of papaverine hydrochloride and the biopharmaceutics of its oral dosage forms. Int J Clin Pharmacol 16: 193–208 Holley FO, Ponganis KV, Stanski DR (1982) Effect of cardiopulmonary bypass on the pharmacokinetics of drugs. Clin Pharmacokinet 7: 234–251 Koska AJ III, Romagnoli A, Kramer WG (1981a) Effect of cardiopulmonary bypass on fentanyl distribution and elimination. Clin Pharmacol Ther 29: 100–105 Koska AJ III, Romagnoli A, Kramer WG (1981b) Pharmacodynamics of fentanyl citrate in patients undergoing aortocoronary bypass. Cardivasc Dis Bull Texas Heart Inst 8: 405–412 Koska AJ, III, Romagnoli A (1981c) Coronary dilators and cardioplegia. Cardiovasc Dis Bull Texas Heart Inst 8: 467–474 Metzler CM, Elfring GL, McEwen AJ (1974) A package of computer programs for pharmacokinetic modeling. Biometrics 30: 562 Pierson SL, Hanigan JJ, Tayler RE, McClurg JE (1979) Simple and rapid high-pressure liquid chromatographic determination of papaverine in plasma. J Pharm Sci 68: 1550–1551 Plachetka JR, Salomon NW, Copeland JG (1981) Plasma propranolol before, during, and after cardiopulmonary bypass. Clin Pharmacol Ther 30: 745–751 Wagner JG (1976) Linear pharmacokinetic equations allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of polyexponential equations which have been fitted to the data. J Pharmacokinet Biopharm 4: 443–467 Wilen G, Ylitalo P (1982) Metabolism of 14C papaverine in man. J Pharm Pharmacol 34: 264–266