The effect of ciprofloxacin on cyclophosphamide pharmacokinetics in patients with non-Hodgkin lymphoma.
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.
Afsharian
Parvaneh
P
Department of Medicine, Division of Hematology, Karolinska Institutet, Huddinge, Stockholm, Sweden.
Möllgård
Lars
L
Hassan
Zuzana
Z
Xie
Hanjing
H
Kimby
Eva
E
Hassan
Moustapha
M
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
D018906:Antineoplastic Agents, Alkylating; D002939:Ciprofloxacin; D003520:Cyclophosphamide