The effect of cimetidine on the pharmacokinetics of epirubicin in patients with advanced breast cancer: preliminary evidence of a potentially common drug interaction.
Epirubicin is known to be metabolized in the liver. Therefore, drugs such as cimetidine, which inhibit the cytochrome P-450 enzyme system or reduce liver blood flow, may reduce the plasma clearance of epirubicin. In a small study, epirubicin 100 mg/m2 every 3 weeks was administered intravenously to eight patients, who also received oral cimetidine (400 mg b.d. for 7 days starting 5 days before chemotherapy) with either the first or second cycles. Epirubicin pharmacokinetics and liver blood flow (idocyanine green clearance) were assessed at each course. The areas under the plasma concentration time curves (AUCs) were used to compare the systemic exposure to epirubicin and its metabolites with each course. The estimated median percentage increase (95% confidence interval CI) in the AUC with cimetidine were: epirubicin 50% (95% CI -18 to 193, epirubicinol 41% (95% CI 1 to 92). Despite the small numbers studied, the increase in the active metabolite epirubicinol was significant (P < 0.05). These changes in exposure were not explained by reduced cytochrome P-450 activity as the 7-deoxy-doxorubicinol aglycone AUC was not reduced (357% increase: 95% CI 17 to 719) or by a decrease in liver blood flow (17% increase: 95% CI -39 to 104). Cimetidine is likely to be coprescribed or self-administered with epirubicin and therefore clinicians should be aware of this potential interaction.
Murray
L S
LS
University of Glasgow, Western Infirmary, UK.
Jodrell
D I
DI
Morrison
J G
JG
Cook
A
A
Kerr
D J
DJ
Whiting
B
B
Kaye
S B
SB
Cassidy
J
J
D000284:Administration, Oral; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000493:pharmacokinetics*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D015251:Epirubicin / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D006635:Histamine H2 Antagonists; D015251:Epirubicin; D002927:Cimetidine; D011239:Prednisolone