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

NCT ID: NCT07113587

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-08
• Study Completion Date: 2017-07-07

Brief 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 (t½), 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.

Conditions

Peritoneal Dialysis-associated Peritonitis; Peritoneal Dialysis (PD); Pharmacokinetics; Intravenous Administration; Intravenous; Meropenem; Intraperitoneal; Ampicillin; Aztreonam; Ciprofloxacin; Minimum Inhibitory Concentration (MIC)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ampicillin in APD patients without peritonitis

Group Type: EXPERIMENTAL

Application of intraperitoneal and intravenous ampicillin in automated peritoneal dialysis patients without peritonitis

Intervention Type: DRUG

meropenem in APD patients without peritonitis

Group Type: EXPERIMENTAL

Application of intraperitoneal and intravenous meropenem in in automated peritoneal dialysis patients without peritonitis

Intervention Type: DRUG

ciprofloxacin in APD patients without peritonitis

Group Type: EXPERIMENTAL

Application of intraperitoneal and intravenous ciprofloxacin in automated peritoneal dialysis patients without peritonitis

Intervention Type: DRUG

aztreonam in APD patients without peritonitis

Group Type: EXPERIMENTAL

Application of intraperitoneal and intravenous aztreonam in automated peritoneal dialysis patients without peritonitis

Intervention Type: DRUG

Interventions

Application of intraperitoneal and intravenous meropenem in in automated peritoneal dialysis patients without peritonitis

Intervention Type: DRUG

Application of intraperitoneal and intravenous ampicillin in automated peritoneal dialysis patients without peritonitis

Intervention Type: DRUG

Application of intraperitoneal and intravenous aztreonam in automated peritoneal dialysis patients without peritonitis

Intervention Type: DRUG

Application of intraperitoneal and intravenous ciprofloxacin in automated peritoneal dialysis patients without peritonitis

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adults aged 18-85 on APD using icodextrin.
• Informed consent provided.
• No recent infections or antibiotic use.

Exclusion Criteria

• Active systemic infection or recent peritonitis.
• Severe liver disease, pregnancy, allergy to study drugs.
• Hemoglobin <9 g/dL; BMI <19 or >35.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Karl Landsteiner University of Health Sciences

OTHER

Sponsor Role: collaborator

University of Vienna

OTHER

Sponsor Role: collaborator

Medical University of Cologne

OTHER

Sponsor Role: collaborator

Karl Landsteiner Insitute for Nephrology and Haemato-Oncology

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin Wiesholzer, MD

Role: PRINCIPAL_INVESTIGATOR

UK St. Pölten - Deparment of Internal Medicine 1, Nephrology

Locations

UK St. Pölten

Sankt Pölten, , Austria

Countries

Austria

References

Hextall A, Andrews JM, Donovan IA, Wise R. Intraperitoneal penetration of meropenem. J Antimicrob Chemother. 1991 Aug;28(2):314-6. doi: 10.1093/jac/28.2.314. No abstract available.

Reference Type: BACKGROUND

PMID: 1778863 (View on PubMed)

Manley HJ, Bailie GR. Treatment of peritonitis in APD: pharmacokinetic principles. Semin Dial. 2002 Nov-Dec;15(6):418-21. doi: 10.1046/j.1525-139x.2002.00103.x.

Reference Type: BACKGROUND

PMID: 12437537 (View on PubMed)

Van Ende C, Tintillier M, Cuvelier C, Migali G, Pochet JM. Intraperitoneal meropenem administration: a possible alternative to the intravenous route. Perit Dial Int. 2010 Mar-Apr;30(2):250-1. doi: 10.3747/pdi.2009.00052. No abstract available.

Reference Type: BACKGROUND

PMID: 20200373 (View on PubMed)

Warady BA, Bakkaloglu S, Newland J, Cantwell M, Verrina E, Neu A, Chadha V, Yap HK, Schaefer F. Consensus guidelines for the prevention and treatment of catheter-related infections and peritonitis in pediatric patients receiving peritoneal dialysis: 2012 update. Perit Dial Int. 2012 Jun;32 Suppl 2(Suppl 2):S32-86. doi: 10.3747/pdi.2011.00091. No abstract available.

Reference Type: BACKGROUND

PMID: 22851742 (View on PubMed)

Li PK, Szeto CC, Piraino B, Bernardini J, Figueiredo AE, Gupta A, Johnson DW, Kuijper EJ, Lye WC, Salzer W, Schaefer F, Struijk DG; International Society for Peritoneal Dialysis. Peritoneal dialysis-related infections recommendations: 2010 update. Perit Dial Int. 2010 Jul-Aug;30(4):393-423. doi: 10.3747/pdi.2010.00049. No abstract available.

Reference Type: BACKGROUND

PMID: 20628102 (View on PubMed)

Salzer W. Antimicrobial-resistant gram-positive bacteria in PD peritonitis and the newer antibiotics used to treat them. Perit Dial Int. 2005 Jul-Aug;25(4):313-9.

Reference Type: BACKGROUND

PMID: 16022084 (View on PubMed)

Other Identifiers

2013-004985-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS4-EK-2/301-2013

Identifier Type: -

Identifier Source: org_study_id