Summary
Phenprocoumon was given orally to 9 patients with biopsy proven liver cirrhosis (dose range 0.12–0.25 mg/kg) and to 7 healthy volunteers (0.23 mg/kg). Concentrations of phenprocoumon were determined using HPLC in plasma and urine samples obtained for 6–7 days after drug administration. The binding of [3H]-phenprocoumon in plasma from all subjects was determined by equilibrium dialysis. Antipyrine plasma concentrations were determined spectrophotometrically following oral administration of antipyrine (1200 mg). The total body clearance of phenprocoumon was higher in the cirrhotic patients (1.64±0.16 ml/h/kg mean ± SEM) than in the healthy volunteers (0.90±0.07 ml/h/kg), however the free drug clearance was not significantly different in the patients (144±14 ml/h/kg) compared with normal (113±11 ml/h/kg). In contrast the clearance of antipyrine was much reduced in the cirrhotic group (17.5±2.9 ml/h/kg) compared with normal (35.6±3.9 ml/h/kg). The metabolic clearance of phenprocoumon via glucuronidation, is relatively unaffected during cirrhosis compared with antipyrine clearance via oxidation.
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References
Andreasen PB, Ranek L, Statland BE, Tygstrup N (1974) Clearance of antipyrine. Dependence of quantitative liver function. Europ J Clin Invest 4: 129–134
Brodie BB, Axelrod J, Soberman R, Levy BB (1949) The estimation of antipyrine in biological materials. J Biol Chem 179: 25–29
Heni G, Lehnhardt G, Glogner P (1976) Eliminationkinetik von Phenprocoumon (Marcumar) bei Leberzirrhose und nach Vorbehandlung mit Phenobarbital. Int J Clin Pharmacol 13: 253–261
Kitteringham NR, Büstgens L, Brundert E, Mineshita S, Ohnhaus EE (1983) Pharmacokinetics of phenprocoun in patients with liver cirrhosis. Br J Clin Pharmacol 15: 590 P
Klotz U, Fischer C, Müller-Seydlitz P, Schulz J, Müller WA (1979) Alterations in the disposition of differently cleared drugs in patients with cirrhosis. Clin Pharmacol Ther 26: 221–227
Koch-Weser J, Sellers EM (1971) Drug interactions with coumarin anticoagulants. New Engl J Med 285: 487–498
Kraus JW, Desmond PV, Marshall SP, Johnson RF, Schenker S, Wilkinson GR (1978) Effects of aging and liver disease on disposition of lorazepam. Clin Pharmacol Ther 24: 411–419
Meinertz Th, Gilfrich HJ, Groth U, Jonen HG, Jähnchen E (1977) Interruption of the enterohepatic circulation of phenprocoumon by cholestyramine. Clin Pharmacol Ther 21: 731–735
Ohnhaus EE, Münch U, Meier J (1976) Vergleichende Untersuchung zur Elimination von Pindolol und Antipyrin bei Patienten mit Lebererkrankungen. Schweiz Med Wochenschr 106: 1748–1750
Ohnhaus EE, Münch U, Meier J (1982) Elimination of pindolol in liver disease. Eur J Clin Pharmacol 22: 247–251
Sellers EM, Greenblatt DJ, Giles HC, Narango CA, Kaplan H, McLeod SM (1979) Chlordiazepoxide and oxazepam diposition in cirrhosis. Clin Pharmacol Ther 26: 240–246
Shull HJ, Wilkinson GR, Johnson R, Schenker S (1976) Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med 84: 420–425
Sotaniemi EA, Anttila M, Pelkonen OR, Järvensivu P, Sundquist A (1979) Plasma clearance of propranolol and sotalol and hepatic drug metabolizing enzyme activity. Clin Pharmacol Ther 26: 153–161
Tschanz C, Wilson RL, Shand DG (1983) The effects of cirrhosis on temazepam elimination. Clin Pharmacol Ther 33: 218
Vesell ES (1979) The antipyrine test in clinical pharmacology: conceptions and misconceptions. Clin Pharmacol Ther 26: 275–286
Williams RL, Blaschke TF, Meffin PJ, Melmon KL, Rowland M (1977) Influence of acute viral hepatitis on disposition and plasma binding of tolbutamide. Clin Pharmacol Ther 21: 301–309
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Kitteringham, N.R., Büstgens, L., Brundert, E. et al. The effect of liver cirrhosis on the pharmacokinetics of phenprocoumon. Eur J Clin Pharmacol 26, 65–70 (1984). https://doi.org/10.1007/BF00546711
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DOI: https://doi.org/10.1007/BF00546711