caa a22 4500 397592280 CHVBK 20180308164942.0 cr unu---uuuuu 161202e199605 xx s 000 0 eng 10.1093/jac/37.5.965 doi (NATIONALLICENCE)oxford-10.1093/jac/37.5.965 Pharmacokinetics of netivudine, a potent anti-varicella zoster virus drug, in patients with renal impairment [Elektronische Daten] [J. P. Fillastre, M. Godin, B. Legallicier, P. Chretien, R. Bidault, C. GillotiiT, R. Wooton, J. Posner, R. W. Peck] The pharmacokinetics of a single oral 200 mg dose of netivudine (1-(β-D-arabino-furanosyl)-5-(1-propynyl)uracil), a nucleoside analogue under development for use in varicella zoster virus infections, were studied in 12 renal failure (RF) subjects (creatinine clearance 15±7mL/min) and 12 age-matched healthy subjects with normal creatinine clearance. Blood and urine samples were collected up to nine days after drug administration. Concentrations of netivudine and of its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5 PU), were determined by a specific high performance liquid chromatography assay. The mean peak plasma concentrations of netivudine, Tmax and volume of distribution were not significantly affected by RF. The elimination half-life of netivudine was approximately 15 h in subjects with normal renal function and 60 h in RF patients. Plasma and renal clearances of netivudine were significantly reduced in RF patients and AUC was three to four times higher in these patients. Cmax and AUC of 5 PU were higher in RF patients, and the half-life was also significantly longer. However, the half-life of this metabolite was much lower than that of the parent compound. Tmax and the lag time were similar in the two groups. There were highly significant correlations for netivudine and 5 PU between half-life and creatinine clearance and between renal clearance and creatinine clearance. These findings suggest that netivudine dosage may need to be reduced in patients with severe renal failure, and confirm that formation of the 5 PU is independent of the elimination of netivudine from plasma. © 1996 The British Society for Antimicrobial Chemotherapy Original articles nationallicence Fillastre J. P. Department of Nephrology, University of Rouen France aut Godin M. Department of Nephrology, University of Rouen France aut Legallicier B. Department of Nephrology, University of Rouen France aut Chretien P. C EM AX Lab. rue Maréchal Juin Rouen France aut Bidault R. Laboratoires Wellcome 92442 Issy-les-Moulineaux cedex, France aut GillotiiT C. Laboratoires Wellcome 92442 Issy-les-Moulineaux cedex, France aut Wooton R. The Wellcome Research Laboratories Beckenham, UK aut Posner J. The Wellcome Research Laboratories Beckenham, UK aut Peck R. W. The Wellcome Research Laboratories Beckenham, UK aut Journal of Antimicrobial Chemotherapy Oxford University Press 37/5(1996-05), 965-974 0305-7453 37:5<965 1996 37 jac https://doi.org/10.1093/jac/37.5.965 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/37.5.965 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fillastre J. P. Department of Nephrology, University of Rouen France aut NATIONALLICENCE 700 1- Godin M. Department of Nephrology, University of Rouen France aut NATIONALLICENCE 700 1- Legallicier B. Department of Nephrology, University of Rouen France aut NATIONALLICENCE 700 1- Chretien P. C EM AX Lab. rue Maréchal Juin Rouen France aut NATIONALLICENCE 700 1- Bidault R. Laboratoires Wellcome 92442 Issy-les-Moulineaux cedex, France aut NATIONALLICENCE 700 1- GillotiiT C. Laboratoires Wellcome 92442 Issy-les-Moulineaux cedex, France aut NATIONALLICENCE 700 1- Wooton R. The Wellcome Research Laboratories Beckenham, UK aut NATIONALLICENCE 700 1- Posner J. The Wellcome Research Laboratories Beckenham, UK aut NATIONALLICENCE 700 1- Peck R. W. The Wellcome Research Laboratories Beckenham, UK aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 37/5(1996-05), 965-974 0305-7453 37:5<965 1996 37 jac Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford