The influence of cimetidine on the pharmacokinetics of 5-fluorouracil.

The influence of cimetidine pretreatment on the pharmacokinetics of 5-fluorouracil (5FU) has been studied in 15 ambulant patients with carcinoma. Neither pretreatment with a single dose of cimetidine (400 mg) nor with daily treatment at 1000 mg for 1 week altered 5FU pharmacokinetics. Pretreatment with cimetidine for 4 weeks (1000 mg daily) led to increased peak plasma concentrations of 5FU and also area under the plasma concentration-time curve (AUC). The peak plasma concentration after oral 5FU was increased by 74% from 18.7 +/- 4.5 micrograms/ml (mean +/- s.e. mean) to 32.6 +/- 4.4 micrograms/ml (P less than 0.05) and AUC was increased by 72% from 528 +/- 133 micrograms/ml-1 min (mean +/- s.e. mean) to 911 +/- 152 micrograms ml-1 min (P less than 0.05). After intravenous 5FU, AUC was increased by 27% from 977 +/- 96 micrograms ml-1 min (mean +/- s.e. mean) to 1353 +/- 124 micrograms ml-1 min (P less than 0.01). Total body clearance for 5FU following intravenous administration was decreased by 28% from 987 +/- 116 ml/min (mean +/- s.e. mean) to 711 +/- 87 ml/min (P less than 0.01). The elimination half-life of 5FU was not altered by cimetidine. The basis of the interaction between 5FU and cimetidine is uncertain but probably a combination of inhibited drug metabolism and reduced liver blood flow. The therapeutic implications are considerable and additional care should be taken in patients receiving the two drugs concomitantly.

[1]  R. Murphy,et al.  Pharmacokinetic rationale for the interaction of 5-fluorouracil and misonidazole in humans. , 1983, British Journal of Cancer.

[2]  W. Kirch,et al.  Influence of ranitidine on plasma metoprolol and atenolol concentrations. , 1983, British medical journal.

[3]  A Johnston,et al.  STRIPE: an interactive computer program for the analysis of drug pharmacokinetics. , 1983, Journal of pharmacological methods.

[4]  J. Freston.  Drugs Five Years Later: Cimetidine: I. Developments, Pharmacology, and Efficacy , 1982 .

[5]  A. Wood,et al.  Effects of cimetidine on the elimination and actions of ethanol. , 1982, JAMA.

[6]  G. Wilkinson,et al.  Increased toxicity and reduced clearance of lidocaine by cimetidine. , 1982, Annals of internal medicine.

[7]  D. Alberts,et al.  Cimetidine enhancement of cyclophosphamide antitumour activity. , 1982, British Journal of Cancer.

[8]  S. Schenker,et al.  Inhibition of microsomal drug metabolism by histamine H2-receptor antagonists studied in vivo and in vitro in rodents , 1982 .

[9]  R. Knodell,et al.  Drug metabolism by rat and human hepatic microsomes in response to interaction with H2-receptor antagonists , 1982 .

[10]  J. Freston.  Cimetidine. I. Developments, pharmacology, and efficacy. , 1982, Annals of internal medicine.

[11]  T. Schwinghammer,et al.  Drug interactions with cimetidine. , 1981, American journal of hospital pharmacy.

[12]  U. Klotz,et al.  Cimetidine increases steady state plasma levels of propranolol. , 1981, British journal of clinical pharmacology.

[13]  Jerome J. Schentag,et al.  Alteration of theophylline clearance and half-life by cimetidine in normal volunteers. , 1981, Annals of internal medicine.

[14]  U. Klotz,et al.  Elevation of steady‐state diazepam levels by cimetidine , 1981, Clinical pharmacology and therapeutics.

[15]  J. Plachetka,et al.  Cimetidine decreases theophylline clearance. , 1981, Annals of internal medicine.

[16]  A. Heagerty,et al.  Influence of cimetidine on pharmacokinetics of propranolol. , 1981, British medical journal.

[17]  G. Wilkinson,et al.  Reduction of liver blood flow and propranolol metabolism by cimetidine. , 1981, The New England journal of medicine.

[18]  E. Weiss,et al.  Intralesional 5-Fluorouracil: A Therapy for Solitary Infantile Myofibromatosis , 2023, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[19]  A. Howell,et al.  Pharmacokinetics of oral and intravenous fluorouracil in humans. , 1980, Journal of pharmaceutical sciences.

[20]  I. Macdonald,et al.  Cimetidine and ranitidine: comparison of effects on hepatic drug metabolism. , 1980, British medical journal.

[21]  R. Dedrick,et al.  Nonlinear pharmacokinetic models for 5‐fluorouracil in man: Intravenous and intraperitoneal routes , 1980, Clinical pharmacology and therapeutics.

[22]  A. Breckenridge,et al.  CIMETIDINE: INTERACTION WITH ORAL ANTICOAGULANTS IN MAN , 1979, The Lancet.

[23]  A. Lant,et al.  Plasma levels of 5-fluorouracil after oral and intravenous administration in cancer patients. , 1979, British journal of clinical pharmacology.

[24]  M. Hughes,et al.  LIVER ALCOHOL AND ALDEHYDE DEHYDROGENASE: INHIBITION AND POTENTIATION BY HISTAMINE AGONISTS AND ANTAGONISTS , 1979, Clinical and experimental pharmacology & physiology.

[25]  G. Ramírez,et al.  A phase III study comparing the clinical utility of four regimens of 5‐Fluorouracil. A preliminary report , 1977, Cancer.

[26]  Grant R. Wilkinson,et al.  A physiological approach to hepatic drug clearance , 1975 .

[27]  J. Bateman,et al.  5-Fluorouracil (NSC-19893) therapy for pancreatic carcinoma: comparison of oral and intravenous routes. , 1975, Cancer chemotherapy reports.

[28]  W. Sadee,et al.  Determination of 5-fluorouracil (NSC-19893) plasma levels in rats and man by isotope dilution-mass fragmentography. , 1975, Cancer chemotherapy reports.

[29]  L. Irwin,et al.  Clinical pharmacology of oral and intravenous 5-fluorouracil (NSC-19893). , 1974, Cancer chemotherapy reports.