Influence of a 3-day regimen of azithromycin on the disposition kinetics of cyclosporine A in stable renal transplant patients.
Some macrolide antibiotics have been shown to produce significant drug-drug interactions through the inhibition of cytochrome P450 (CYP) enzymes. In renal transplant patients these interactions pose potentially serious problems for the safe administration of cyclosporine A (CSA), a substrate of CYP3A4. The effects of azithromycin on CSA disposition kinetics were evaluated in eight stable renal transplant patients. Patients had been stabilized on individualized doses of CSA which remained unchanged throughout the study. Azithromycin was administered for 3 days. Baseline measurements of CSA disposition kinetics were taken prior to azithromycin treatment (study day 2) and after 3 days (study day 5) of azithromycin treatment (500mg/day, orally). The key parameters of interest were the area under the CSA blood concentration versus time curve (AUC) measured for 24h after the morning dose of CSA on both days 2 and 5, and the C(max) values of CSA. The geometric mean ratios (GMRs) of those parameters (day 5/day 2) and their 90% confidence intervals (90% CI) were 107 (98,116) and 119 (104,136), respectively. The 7% increase in exposure level and 19% increase in peak plasma concentration are not likely to be clinically significant. It is concluded that azithromycin (500mg/dayx3 days) does not alter the disposition kinetics of CSA in a clinically significant way, and that CSA dosage adjustments are not warranted in renal transplant patients taking these two drugs together.
Department of Pharmacology, Center for Applied Pharmacology, The University of Toledo, 2801 W. Bancroft St., Toledo, OH 43606, USA. Kbachma@utnet.utoledo.edu
Kenneth
K
Bachmann
Luis
L
Jauregui
Richa
R
Chandra
Kamlesh
K
Thakker
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017963:Azithromycin / Q000494:pharmacology* / Q000627:therapeutic use; D002853:Chromatography, Liquid; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D013058:Mass Spectrometry
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D017963:Azithromycin; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human