Summary
Twenty one patients with liver disease (cirrhosis 11, chronic hepatitis 5 and acute hepatitis 5) and 6 healthy volunteers were given a single i.v. dose of nitrendipine 5 mg. Afterwords nitrendipine 20 mg once daily were administered orally for seven days.
With the intravenous injection a significant increase in the AUC and elimination half-life of nitrendipine was found in patients with cirrhosis as compared to the normal volunteers. After chronic oral dosing, the area under the plasma concentration-time curve, AUC (0–24), was 94.5 ng ml−1 h and the plasma clearance CL was 1380.6 ml/min in the healthy controls; in patients with cirrhosis the AUC (0–24) h was significantly greater at 309.4 ng ml−1 h and CL had fallen to 686.6 ml/min. Considerable accumulation of nitrendipine was also found in the patients with chronic hepatitis. Nitrendipine could not be detected in urine from any of the subjects. Blood pressure and heart rate were not significantly influenced by the treatment in the various groups investigated. Antipyrine clearance in the patients with cirrhosis was correlated with the nitrendipine plasma clearance.
Thus, accumulation of nitrendipine has been demonstrated in the patients with cirrhosis and chronic hepatitis.
Similar content being viewed by others
References
Andreasen PB, Ranek L, Statland BE, Tygstrup N (1974) Clearance of antipyrine dependence of quantitative liver function. Eur J Clin Invest 4: 129–134
Aronoff GR (1984) Pharmacokinetics of nitrendipine in patients with renal failure: Comparison to normal subjects. J Cardiovasc Pharmacol 6: 974S-876S
Eichelbaum M, Spahnbrucker N, (1977) Rapid and sensitive method for the determination of antipyrine in biological fluids by high pressure liquid tomatography. J Chromatogr 140: 288–292
Eichelbaum M, Somogyi A, (1981) Verapamil distribution in health and the diseased state. In: Zancchetti A, Krikler DM (eds) Calcium antagonism in cardiovascular therapy: Experience with verapamil. Excerpta Medica, Amsterdam Oxford Princeton, pp 64–73
Hermsmeyer K, (1983) Might nitrendipine enhance Ca2+ transport in vascular muscle? In: Merrill G, Weiss G (eds) Calcium entry blockers, adenosine and neurohumors. Urban & Schwarzenberg. Baltimore, pp 51–61
Janis RA, Sarmiento JG, Maurer SC, Bolger GT, Triggle DJ (1984) Characteristics of the binding of (3H) nitrendipine to rabbit ventricular membranes: Modification by other Ca2+ channel antagonists and by the Ca2+ channel antagonist, BAY K 8644. J Pharmacol Exp Ther 231: 8–15
Kann J, Krol GJ, Raemsch KD, Burkholder DE, Levitt MJ (1984) Bioequivalence and metabolism of nitrendipine administered orally to healthy volunteers. J Cardiovasc Pharmacol 6: 968S-973S
Kazda S, Garthoff B, Knorr A (1983) Nitrendipine and other calcium entry blockers (calcium antagonists) in hypertension. Fed Proc 42: 46–50
Kirch W, Schäfer-Korting M, Mutschler E, Ohnhaus EE, Braun W (1983) Clinical experience with atenolol in patients with chronic liver disease. J Clin Pharmacol 23: 171–177
Kirch W, Hutt HJ, Heidemann H, Rämsch K, Janisch HD, Ohnhaus EE (1984) Drug interactions with nitrendipine. J Cardiovasc Pharmacol 6: 982S-985S
Kirch W, Ohnhaus EE, Dylewicz P, Pabst J, Storstein L (1986) Bioavailability and elimination of digitoxin in patients with hepatorenal insufficiency. Am Heart J 111: 325–329
Lasseter KC, Shamblen EC, Murdoch AA, Burkholder DE, Krol GJ, Taylor Jr RJ, Vanov SK (1984) Steady-state pharmacokinetics of nitrendipine in hepatic insufficiency. J Cardiovasc Pharmacol 6: 977S-981S
Lewis GP, Jusko WJ (1975) Pharmacokinetics of ampicillin in cirrhosis. Clin Pharmacol Ther 18: 475–479
Mawer GE, Millier NE, Turnberg LA (1972) Metabolism of amylobarbitone in patients with chronic liver disease. Br J Pharmacol 44: 549–552
Ohnhaus EE, Kirchhof B, Penheim E (1979) Effect of enzyme induction on plasma lipids using antipyrine, phenobarbital and rifampicin. Clin Pharmacol Ther 25: 591–597
Ohnhaus EE, Münch U, Meier J (1982) Elimination of pindolol in liver disease. Eur J Clin Pharmacol 22: 247–251
Raemsch KD, Sommer J (1984) Pharmacokinetics and metabolism of nitrendipine. In: Scriabine A, Vanov S, Deck K (eds) Nitrendipine. Urban & Schwarzeberg, Baltimore, pp 409–421
Sachs L (1984) Angewandte Statistik, 6th edn. Springer, Berlin Heidelberg New York
Scriabine A, Johnson CE, Steinsland O (1982) Antagonism of Ca2+-induced contractions of rabbit ear artery by nitrendipine and reversal of this effect by norepinephrine. Fed Proc 41: 1482–1484
Thompson EN, Williams R (1965) Effect of age upon liver function with particular reference to bromsulphthalein excretion. Gut 6: 266–270
Thomson PD, Melmon KL, Richardson JA, Cohn K, Steinbrunn W, Cudihee R, Rowland M (1973) Lidocaine pharmacokinetics in advanced heart failure, liver disease and renal failure in humans. Ann Intern Med 78: 499–502
Wagner JG (1975) Fundamentals of clinical pharmacokinetics. Drug Intellegene Publications, Hamilton, Illinois
Zilly W (1979) Digitoxin bei akuter und chronischer Leberinsuffizienz. In: Greeff K, Rietbrock N (eds) Digitoxin als Alternative in der Therapie der Herzinsuffizienz. Schattauer, Stuttgart
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dylewicz, P., Kirch, W., Santos, S.R. et al. Bioavailability and elimination of nitrendipine in liver disease. Eur J Clin Pharmacol 32, 563–568 (1987). https://doi.org/10.1007/BF02455989
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02455989