Angiotensin Converting Enzyme Inhibitors (ACEI) and doxorubicin pharmacokinetics in women receiving adjuvant breast cancer treatment

Anne Blaes, Daniel Duprez, Todd Defor, Ryan Shanley, Heather Beckwith, Tufia C Haddad, David Potter, Douglas Yee, Kinjal Sanghavi, Pamala Jacobson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: Doxorubicin (DOX) chemotherapy can cause cardiac complications. Angiotensin converting enzyme inhibitors (ACEI) may protect against these complications. We performed a pharmacokinetics (PK) study to determine whether DOX levels are altered in the presence of ACEI. Methods: In this randomized, cross-over, single-blinded drug-drug interaction study, 19 women with breast cancer prescribed DOX and cyclophosphamide every 14 days received one cycle of DOX chemotherapy with ACEI enalapril 10 mg daily and another cycle of DOX with placebo. Blood samples for DOX and doxorubicinol were drawn at baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion with and without ACEI enalapril. Correlative laboratories were also obtained. PK data was analyzed using non compartmental methods and DOX and doxorubicinol area under the curve (AUC) 0 to infinity, Cmax and half-life were estimated. Paired t-tests were used to determine whether DOX and its metabolite were altered with the use of enalapril (P < 0.05). Results: 17 women (median age 45 years) received 60 mg/m2 DOX every two weeks for four cycles. Mean (SD) AUC0- ∞ for DOX and doxorubicinol with enalapril exposure was 1185.56 (44.64) hr*ng/ml and 1040 (80.6) hr*ng/ml, respectively. AUC0- ∞ for DOX and doxobubicinol without enalapril was 1167.73 (45.26) hr*ng/ml and 1056.32 (92.03) hr*ng/ml, respectively. There is no interaction between DOX and enalapril. Enalapril was tolerated (33% grade 1 dizziness). Conclusion: ACEI, enalapril, does not appear to alter the PK of DOX. Ongoing efforts to determine the effectiveness of ACEI as a cardioprotective agent in women receiving DOX chemotherapy should be continued.

Original languageEnglish (US)
Article number32
JournalSpringerPlus
Volume4
Issue number1
DOIs
StatePublished - Dec 30 2015

Fingerprint

Angiotensin-Converting Enzyme Inhibitors
Doxorubicin
Pharmacokinetics
Enalapril
Breast Neoplasms
Therapeutics
Drug Therapy
Cardiotonic Agents
Dizziness
Drug Interactions
Cyclophosphamide
Area Under Curve
Half-Life
Placebos

Keywords

  • Angiotensin Converting Enzyme Inhibitors
  • Breast cancer
  • Cardioprotection
  • Doxorubicin
  • Drug interaction
  • Enalapril
  • Pharmacokinetics

ASJC Scopus subject areas

  • General

Cite this

Angiotensin Converting Enzyme Inhibitors (ACEI) and doxorubicin pharmacokinetics in women receiving adjuvant breast cancer treatment. / Blaes, Anne; Duprez, Daniel; Defor, Todd; Shanley, Ryan; Beckwith, Heather; Haddad, Tufia C; Potter, David; Yee, Douglas; Sanghavi, Kinjal; Jacobson, Pamala.

In: SpringerPlus, Vol. 4, No. 1, 32, 30.12.2015.

Research output: Contribution to journalArticle

Blaes, A, Duprez, D, Defor, T, Shanley, R, Beckwith, H, Haddad, TC, Potter, D, Yee, D, Sanghavi, K & Jacobson, P 2015, 'Angiotensin Converting Enzyme Inhibitors (ACEI) and doxorubicin pharmacokinetics in women receiving adjuvant breast cancer treatment', SpringerPlus, vol. 4, no. 1, 32. https://doi.org/10.1186/s40064-015-0802-4
Blaes, Anne ; Duprez, Daniel ; Defor, Todd ; Shanley, Ryan ; Beckwith, Heather ; Haddad, Tufia C ; Potter, David ; Yee, Douglas ; Sanghavi, Kinjal ; Jacobson, Pamala. / Angiotensin Converting Enzyme Inhibitors (ACEI) and doxorubicin pharmacokinetics in women receiving adjuvant breast cancer treatment. In: SpringerPlus. 2015 ; Vol. 4, No. 1.
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abstract = "Purpose: Doxorubicin (DOX) chemotherapy can cause cardiac complications. Angiotensin converting enzyme inhibitors (ACEI) may protect against these complications. We performed a pharmacokinetics (PK) study to determine whether DOX levels are altered in the presence of ACEI. Methods: In this randomized, cross-over, single-blinded drug-drug interaction study, 19 women with breast cancer prescribed DOX and cyclophosphamide every 14 days received one cycle of DOX chemotherapy with ACEI enalapril 10 mg daily and another cycle of DOX with placebo. Blood samples for DOX and doxorubicinol were drawn at baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion with and without ACEI enalapril. Correlative laboratories were also obtained. PK data was analyzed using non compartmental methods and DOX and doxorubicinol area under the curve (AUC) 0 to infinity, Cmax and half-life were estimated. Paired t-tests were used to determine whether DOX and its metabolite were altered with the use of enalapril (P < 0.05). Results: 17 women (median age 45 years) received 60 mg/m2 DOX every two weeks for four cycles. Mean (SD) AUC0- ∞ for DOX and doxorubicinol with enalapril exposure was 1185.56 (44.64) hr*ng/ml and 1040 (80.6) hr*ng/ml, respectively. AUC0- ∞ for DOX and doxobubicinol without enalapril was 1167.73 (45.26) hr*ng/ml and 1056.32 (92.03) hr*ng/ml, respectively. There is no interaction between DOX and enalapril. Enalapril was tolerated (33{\%} grade 1 dizziness). Conclusion: ACEI, enalapril, does not appear to alter the PK of DOX. Ongoing efforts to determine the effectiveness of ACEI as a cardioprotective agent in women receiving DOX chemotherapy should be continued.",
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AU - Duprez, Daniel

AU - Defor, Todd

AU - Shanley, Ryan

AU - Beckwith, Heather

AU - Haddad, Tufia C

AU - Potter, David

AU - Yee, Douglas

AU - Sanghavi, Kinjal

AU - Jacobson, Pamala

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N2 - Purpose: Doxorubicin (DOX) chemotherapy can cause cardiac complications. Angiotensin converting enzyme inhibitors (ACEI) may protect against these complications. We performed a pharmacokinetics (PK) study to determine whether DOX levels are altered in the presence of ACEI. Methods: In this randomized, cross-over, single-blinded drug-drug interaction study, 19 women with breast cancer prescribed DOX and cyclophosphamide every 14 days received one cycle of DOX chemotherapy with ACEI enalapril 10 mg daily and another cycle of DOX with placebo. Blood samples for DOX and doxorubicinol were drawn at baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion with and without ACEI enalapril. Correlative laboratories were also obtained. PK data was analyzed using non compartmental methods and DOX and doxorubicinol area under the curve (AUC) 0 to infinity, Cmax and half-life were estimated. Paired t-tests were used to determine whether DOX and its metabolite were altered with the use of enalapril (P < 0.05). Results: 17 women (median age 45 years) received 60 mg/m2 DOX every two weeks for four cycles. Mean (SD) AUC0- ∞ for DOX and doxorubicinol with enalapril exposure was 1185.56 (44.64) hr*ng/ml and 1040 (80.6) hr*ng/ml, respectively. AUC0- ∞ for DOX and doxobubicinol without enalapril was 1167.73 (45.26) hr*ng/ml and 1056.32 (92.03) hr*ng/ml, respectively. There is no interaction between DOX and enalapril. Enalapril was tolerated (33% grade 1 dizziness). Conclusion: ACEI, enalapril, does not appear to alter the PK of DOX. Ongoing efforts to determine the effectiveness of ACEI as a cardioprotective agent in women receiving DOX chemotherapy should be continued.

AB - Purpose: Doxorubicin (DOX) chemotherapy can cause cardiac complications. Angiotensin converting enzyme inhibitors (ACEI) may protect against these complications. We performed a pharmacokinetics (PK) study to determine whether DOX levels are altered in the presence of ACEI. Methods: In this randomized, cross-over, single-blinded drug-drug interaction study, 19 women with breast cancer prescribed DOX and cyclophosphamide every 14 days received one cycle of DOX chemotherapy with ACEI enalapril 10 mg daily and another cycle of DOX with placebo. Blood samples for DOX and doxorubicinol were drawn at baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion with and without ACEI enalapril. Correlative laboratories were also obtained. PK data was analyzed using non compartmental methods and DOX and doxorubicinol area under the curve (AUC) 0 to infinity, Cmax and half-life were estimated. Paired t-tests were used to determine whether DOX and its metabolite were altered with the use of enalapril (P < 0.05). Results: 17 women (median age 45 years) received 60 mg/m2 DOX every two weeks for four cycles. Mean (SD) AUC0- ∞ for DOX and doxorubicinol with enalapril exposure was 1185.56 (44.64) hr*ng/ml and 1040 (80.6) hr*ng/ml, respectively. AUC0- ∞ for DOX and doxobubicinol without enalapril was 1167.73 (45.26) hr*ng/ml and 1056.32 (92.03) hr*ng/ml, respectively. There is no interaction between DOX and enalapril. Enalapril was tolerated (33% grade 1 dizziness). Conclusion: ACEI, enalapril, does not appear to alter the PK of DOX. Ongoing efforts to determine the effectiveness of ACEI as a cardioprotective agent in women receiving DOX chemotherapy should be continued.

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