Abstract
Objective
To evaluate the effects of nicardipine on hepatic blood flow in patients with recent liver transplants. Secondly, to evaluate the liver extraction of nicardipine in order to determine the influence of liver transplantation on its disposition.
Design
Prospective self-controlled clinical study.
Setting
University hospital intensive care unit.
Patients
Eight patients in the early postoperative period of orthotopic liver transplantation.
Measurements and results
Patients were given 5 mg of i.v. nicardipine. Systemic and splanchnic haemodynamic and metabolic parameters were measured before nicardipine administration (T0) and at 5 min (T1), 30 min (T2), and 120 min (T3) after administration. A catheter was inserted into a hepatic vein to determine the total hepatic blood flow (HBF) and the hepatic extraction coefficient of nicardipine. Nicardipine caused no significant changes in HBF, oxygen delivery, oxygen uptake, hepatic venous oxygen saturation, or the hepatic venous partial pressure of oxygen. Likewise, neither blood lactate concentrations nor arterial and hepatic venous lactate-pyruvate ratios were modified by nicardipine. The hepatic extraction coefficient of nicardipine was approximately 0.70 in the first 3 min after complete infusion, then decreased and remained stable at approximately 0.50, showing a nonlinear first-pass metabolism pattern.
Conclusions
Nicardipine administration after liver transplantation appears to have no deleterious effects on HBF. Nicardipine can be classified as a drug of intermediate hepatic extraction coefficient, whose elimination partly depends on hepatic enzyme activity.
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References
Snyder JV (1989) Postoperative evolution of extrahepatic organ function. Transplant Proc 21: 3508–3510
Wilkinson GR, Shand DG (1975) A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 18: 377–390
Whiting RL (1987) Animal pharmacology of nicardipine and its clinical relevance. Am J Cardiol 59: 3j-8j
Caesar J, Shaldon S, Chiandussi L, Guevara L, Sherlock S (1961) The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function Clin Sci 21: 43–57
Noll F (1974) L-(+)-Lactate. Determination with LDH, GPT and NAD. In: Bergmeyer HU (ed) Methods of enzymatic analysis, 2nd edn. Academic Press, New York, pp 1475–1479
Czok R, Lamprecht W (1974) Pyruvate, Phosphoenolpyruvate and D-glycerate-2-phosphate. In: Bergmeyer HU (ed) Methods of enzymatic analysis, 2nd edn. Academic Press, New York, pp 1446–1451
Wu AT, Massey IJ, Kushinsky S (1987) Capillary column gas chromatographic method using electron-capture detection for the simultaneous determination of nicardipine and its pyridine metabolite II in plasma. J Chromatogr 415: 65–73
Chauvin M, Bonnet F, Montembault C, Levron JC, Viars P (1986) The influence of hepatic plasma flow on alfentanil plasma concentration plateaus achieved with an infusion model in humans: measurement of alfentanil hepatic extraction coefficient. Anesth Analg 65: 99–1003
Gasic S, Korn A, Eichler HG (1987) Diltiazem counteracts digitalis-dependent splanchnic vasoconstriction in man. Int J Clin Pharmacol Ther Toxicol 25: 553–557
Koshy A, Hadengue A, Lee SS, Jiron MI, Lebrec D (1987) Possible deleterious hemodynamic effect of nifedipine on portal hypertension in patients with cirrhosis. Clin Pharmacol Ther 42: 295–298
Reiss WG, Bauer LA, Horn JR, Zierler BK, Easterling TR, Strandness DE (1991) The effects of oral nifedipine on hepatic blood flow in humans. Clin Pharmacol Ther 50: 379–384
Vinel JP, Caucanas JP, Combis JM, Cales P, Voigt JJ, Pascal JP (1989) Verapamil has no effect on porto-hepatic pressure gradient, hepatic blood flow and elimination function of the liver in patients with liver cirrhosis. J Hepatol 8: 302–307
Vanhoutte PM (1981) Different effects of calcium entry blockers on vascular smooth muscle. In: Weiss GB (ed) New perspectives on calcium antagonists. American Physiological Society, Bethesda, pp 109–121
Nonami T, Asahi K, Harada A, Nakao A, Takagir H (1990) Effect of hyperdynamic circulatory support on hepatic hemodynamics, oxygen supply and demand after massive hepatectomy. Surgery 109: 277–283
Schofield PS, Kerbey AL, Sugden MC (1986) Hepatic pyruvate metabolism during liver regeneration after partial hepatectomy in the rat. Int J Biochem 18: 453–458
Guerret M, Cheymol G, Hubert M, Julien-Larose C, Lavène D (1987) Simultaneous study of the pharmocokinetics of intravenous and oral nicardipine using a stable isotope. Eur J Clin Pharmacol 37: 381–385
Baky SH (1985) Nicardipine hydrochloride. In: Scriabine (ed) New drugs annual: cardiovascular drugs. Raven Press, New York, pp 153–172
George CF (1979) Drug kinetics and hepatic blood flow. Clin Pharmacokinet 4: 433–448
Urien S, Albengres E, Comte A, Tillement JP (1985) Plasma protein binding and erythrocyte partitioning of nicardipine in vitro. J Cardiovasc Pharmacol 7: 891–898
Turlapaty P, Vary R, Kaplan JA (1989) Nicardipine, a new intravenous calcium antagonist: a review of its pharmacology, pharmacokinetics, and perioperative application. J Cardiothorac Vasc Anesth 3: 344–355
Hayes PC (1992) Liver disease and drug disposition. Br J Anaesth 68: 459–461
Park GR, Pichard L, Tinel M, Larroque C, Elston A, Domerque J, Dexionne B, Maurel P (1994) What changes drug metabolism in critically ill patients? Anaesthesia 49: 188–191
Davis PJ, Stiller RL, Cook DR, Brandom BW, Davis JE, Scierka AM (1989) Effects of cholestatic hepatic disease and chronic renal failure on alfentanil pharmacokinetics in children. Anesth Analg 68: 579–583
Shelly MP, Cory EP, Park GR (1986) Pharmacokinetics of morphine in two children before and after liver transplantation. Br J Anaesth 58: 1218–1223
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This study was supported by the Institut National de la Santé et de la Recherche Médicale, INSERM, Contrat Normalisé d'Etudes Pilotes en recherche clinique 91 CN 41.
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Raucoules-Aimé, M., Drici, M., Goubaux, B. et al. Intravenous nicardipine does not alter hepatic blood flow after orthotopic liver transplant. Intensive Care Med 22, 420–425 (1996). https://doi.org/10.1007/BF01712158
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DOI: https://doi.org/10.1007/BF01712158