Impact of mucositis on oral bioavailability and systemic exposure of ciprofloxacin Gram-negative infection prophylaxis in patients with haematological malignancies

Rhee, K.P. van; Vroom, S.L. de; Hest, R.M. van; Linden, P.D. van der; Tonino, S.H.; Molendijk, E.; Mathot, R.A.A.; Blijlevens, N.M.A.; Knibbe, C.A.J.; Bruggemann, R.J.M.; Geerlings, S.E.

doi:doi:10.1093/jac/dkac283

Background Patients with haematological malignancies frequently endure neutropenia and gastrointestinal (GI)-mucositis after high-dose chemotherapy. In these patients, ciprofloxacin is used for Gram-negative infection prophylaxis. Objectives We investigate ciprofloxacin pharmacokinetics after oral administration in patients with haematological malignancies and explore the impact of GI-mucositis on oral bioavailability and clearance in order to assure adequate systemic exposure. Methods Adult haematological patients from two Dutch University Medical Centres received 500 mg twice daily oral ciprofloxacin for Gram-negative prophylaxis. The ciprofloxacin plasma concentrations were collected at various timepoints after oral ciprofloxacin administration and at various days after completion of chemotherapy. Data obtained after oral and intravenous ciprofloxacin administration in 28 healthy volunteers without mucositis served as a control group (391 samples). For haematological patients the...Show moreBackground Patients with haematological malignancies frequently endure neutropenia and gastrointestinal (GI)-mucositis after high-dose chemotherapy. In these patients, ciprofloxacin is used for Gram-negative infection prophylaxis. Objectives We investigate ciprofloxacin pharmacokinetics after oral administration in patients with haematological malignancies and explore the impact of GI-mucositis on oral bioavailability and clearance in order to assure adequate systemic exposure. Methods Adult haematological patients from two Dutch University Medical Centres received 500 mg twice daily oral ciprofloxacin for Gram-negative prophylaxis. The ciprofloxacin plasma concentrations were collected at various timepoints after oral ciprofloxacin administration and at various days after completion of chemotherapy. Data obtained after oral and intravenous ciprofloxacin administration in 28 healthy volunteers without mucositis served as a control group (391 samples). For haematological patients the degree of GI-mucositis was assessed using the Daily Gut Score (DGS), plasma citrulline and albumin. Data were analysed by non-linear mixed-effects modelling. Results In total, 250 blood samples were collected in 47 patients with a wide variety of haematological malignancies between 0-30 days after start of chemotherapy. Mucositis was generally mild [DGS median (IQR) 1 (1-1) and citrulline 16 mu mol/L (12-23)]. The time to C-max was slower in haematological patients compared with healthy volunteers although no association with the degree of mucositis (defined as DGS or citrulline) could be identified. Ciprofloxacin bioavailability and clearance were 60% and 33.2 L/h, respectively. Conclusions This study supports oral dosing of ciprofloxacin as Gram-negative infection prophylaxis in haematological patients with mild-to-moderate mucositis capable of oral intake.Show less

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Impact of mucositis on oral bioavailability and systemic exposure of ciprofloxacin Gram-negative infection prophylaxis in patients with haematological malignancies