The effect of ciprofloxacin on cyclophosphamide pharmacokinetics in patients with non-Hodgkin lymphoma

Eur J Haematol. 2005 Sep;75(3):206-11. doi: 10.1111/j.1600-0609.2005.00492.x.

Abstract

Cyclophosphamide (CPA) is widely used in chemotherapy. The CPA is a prodrug that requires metabolic transformation to generate the active metabolite, 4-hydroxy-CPA (4-OH-CPA). Ciprofloxacin (CF) is a fluoroquinolone antibiotic with a broad spectrum that is commonly used in treatment of a variety of infections. It has been reported that prophylactic administration of CF during CPA conditioning was a high-risk factor for relapse in patients undergoing allogeneic bone marrow transplantation. In the present study we investigated the pharmacokinetics of CPA and 4-OH-CPA in eight non-Hodgkin lymphoma (NHL) patients treated with CPA together with or without CF. Clearance and distribution volumes of CPA were significantly (P < 0.01) lower (4.7 L/h and 42.3 L, respectively) when patients were treated with CF prior to CPA compared to that observed when the patients did not receive CF (5.9 L/h and 48.1 L, respectively). No change in the elimination half-life was observed. The CF administration prior to CPA has resulted in significantly (P < 0.01) lower exposure to 4-OH-CPA as expressed as area under the plasma concentration curve (AUC). The metabolic ratio AUC(4-OH-CPA)/AUC(CPA) was lower in all patients treated with CF prior to CPA compared to that observed when patients received CPA only (P = 0.008). Our study showed that CF administration alters CPA kinetics in patients with NHL. Other antibiotics than these contain fluoroquinolones should be used during CPA therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Alkylating / blood
  • Antineoplastic Agents, Alkylating / pharmacokinetics*
  • Area Under Curve
  • Ciprofloxacin / therapeutic use*
  • Cyclophosphamide / blood
  • Cyclophosphamide / pharmacokinetics*
  • Female
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Middle Aged

Substances

  • Antineoplastic Agents, Alkylating
  • Ciprofloxacin
  • Cyclophosphamide