Pharmacokinetics of Intraperitoneal and Intravenous Meropenem, Ampicillin, Aztreonam and Ciprofloxacin in Automated Peritoneal Dialysis Patients Without Peritonitis

• Status: COMPLETED
• Trial end date: 2017-07-07

Summary

This study aims to investigate the pharmacokinetics (PK) and pharmacodynamic (PD) profiles of four commonly used antibiotics - meropenem, ampicillin, aztreonam, and ciprofloxacin - administered via intravenous (i.v.) and intraperitoneal (i.p.) routes in patients undergoing automated peritoneal dialysis (APD) without peritonitis. Existing dosing regimens for APD patients are often extrapolated from continuous ambulatory peritoneal dialysis (CAPD) data, despite notable differences in dialysis dynamics, solute clearance, and drug disposition between the two modalities. This discrepancy may result in subtherapeutic exposure or overtreatment, leading to poor clinical outcomes or drug toxicity.

Automated peritoneal dialysis is characterized by multiple, frequent short cycles of dialysate exchange during the night, along with a prolonged daytime dwell using icodextrin-based solutions. These unique features influence both the systemic absorption and elimination of intraperitoneally administered antibiotics. The pharmacokinetics of these antibiotics in APD patients, particularly with regard to intermittent i.p. dosing, remains insufficiently studied.

This single-center, open-label, randomized crossover study will evaluate plasma, dialysate, and urine concentrations of each antibiotic after both i.v. and i.p. administration in 24 adult patients (6 per drug group) receiving APD. Each subject will receive a single dose of one antibiotic (either 0.5g meropenem, 2g ampicillin, 1g aztreonam, or 400mg ciprofloxacin) via both routes, separated by a one-week washout period. Intraperitoneal administration will occur at the end of the cycler session, allowing the drug to dwell in 1.5L of icodextrin solution during the long daytime exchange.

Serial samples of plasma, peritoneal dialysate, and urine will be collected over a 24-hour period following each drug administration. High-performance liquid chromatography (HPLC) will be used to measure drug concentrations. Pharmacokinetic parameters to be calculated include area under the concentration-time curve (AUC), maximum concentration (Cmax), half-life (t), and time to maximum concentration (Tmax). Secondary PK/PD indices such as time above the minimum inhibitory concentration (T\>MIC) and AUC/MIC ratios will also be assessed to estimate the potential efficacy at the infection site.

The study drugs have well-characterized safety profiles and have been previously used via both i.v. and i.p. routes in CAPD and clinical practice. The study protocol includes safety monitoring, including assessment of adverse events, vital signs, hematology, and clinical chemistry parameters. Risks to subjects are considered minimal, primarily related to venous catheterization and single-dose drug administration. Participants are not expected to receive direct therapeutic benefit but will contribute to the optimization of antimicrobial therapy in APD patients with infections such as peritonitis and pneumonia.

This research addresses a critical gap in evidence-based dosing of antimicrobials in the APD population. Results from this study may inform future clinical guidelines and support rational selection and dosing of antibiotics in peritoneal dialysis-associated infections. It also offers insight into the feasibility of intermittent intraperitoneal therapy in APD patients and the systemic exposure achieved through this route. The study is conducted in accordance with Good Clinical Practice (GCP), the Declaration of Helsinki, and Austrian regulatory and ethical requirements.

• Phase: PHASE2

Details

• Lead Sponsor: Karl Landsteiner Insitute for Nephrology and Haemato-Oncology
• Collaborators: Karl Landsteiner University of Health Sciences; Medical University of Cologne; University of Vienna