Pharmacokinetics of the antimicrobial agents rifampicin and miconazole released from a loaded central venous catheter

• Published in: The Journal of hospital infection Vol. 53; no. 2; pp. 129 - 135
• Main Authors: Rump, A.F.E, Güttler, K, König, D.P, Yücel, N, Korenkov, M, Schierholz, J.M
• Format: Journal Article
• Language: English
• Published: Kent Elsevier Ltd 01-02-2003; Elsevier
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Biological and medical sciences; Biological Availability; Catheterization, Central Venous; Foreign body infection, central venous catheters, pharmacokinetics, antibiotics, miconazole, rifampicin, side effects; Half-Life; Humans; Male; Medical sciences; Miconazole - blood; Miconazole - pharmacokinetics; Middle Aged; Pharmacology. Drug treatments; Rifampin - blood; Rifampin - pharmacokinetics; Foreign body infection, central venous catheters, pharmacokinetics, antibiotics, miconazole, rifampicin, side effects; Imidazole derivatives; Toxicity; Catheter; Foreign body infection; central venous catheters; Antimicrobial agent; Central vein; Antibiotic; Antifungal agent; Rifampicin; Secondary effect; side effects; Antituberculous agent; Foreign body; Antibacterial agent; Miconazole; Pharmacokinetics; antibiotics
• ISSN: 0195-6701; 1532-2939
• DOI: 10.1053/jhin.2002.1358

The time course of rifampicin and miconazole concentrations after insertion of a polyurethane catheter loaded with these antibiotics were studied. Data from controlled release experiments in vitro were used, and the concentration time courses of the antimicrobials in serum were calculated by pharmacokinetic simulations. Systemic therapy using typical dosages (rifampicin 600mg/day iv, miconazole 3×200mg/day iv) results in rifampicin concentrations between 54 and 8424μg/L, and miconazole concentrations between 3567 and 4676μg/L. After insertion of a polyurethane catheter loaded with these antibiotics, the maximal concentrations after catheter placement were determined as 6μg/L at 10.7h for rifampicin, and 13μg/L at 28.6h for miconazole. Assuming that the total amount of antibiotics incorporated in the catheter matrix were bioavailable (‘worst case’), the resulting maximal concentrations calculated by simulation are 10μg/L for rifampicin and 65μg/L for miconazole. Maximal concentrations of rifampicin or miconazole resulting from the insertion of a polyurethane catheter loaded with these antibiotics are, therefore, far below the concentrations resulting from a systemic therapy with the same antimicrobial agents. Even in the worst case, the danger of selecting resistant bacterial strains seems remote because the systemic drug levels are magnitudes of order below subinhibitory concentrations.