{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:06:10Z","timestamp":1784037970719,"version":"3.55.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Valacyclovir, the\n            <jats:sc>l<\/jats:sc>\n            -valyl ester prodrug of acyclovir (ACV), is widely prescribed to treat infections caused by varicella-zoster virus or herpes simplex virus. Rarely, treatment is complicated by reversible neuropsychiatric symptoms. By mechanisms not fully understood, this occurs more frequently in the setting of renal impairment. We characterized the steady-state pharmacokinetics of ACV and its metabolites 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8-hydroxy-acyclovir (8-OH-ACV) in cerebrospinal fluid (CSF) and the systemic circulation. We administered multiple doses of high-dose valacyclovir to 6 subjects with normal renal function and 3 subjects with chronic renal impairment (creatinine clearance [CrCl], \u223c15 to 30 ml\/min). Dosages were 2,000 mg every 6 h and 1,500 mg every 12 h, respectively. Indwelling intrathecal catheters allowed serial CSF sampling throughout the dosing interval. The average steady-state concentrations of acyclovir, CMMG, and 8-OH-ACV were greater in both the systemic circulation and the CSF among subjects with impaired renal function than among subjects with normal renal function. However, the CSF penetration of each analyte, reflected by the CSF-to-plasma area under the concentration-time curve over the 6- or 12-h dosing interval (AUC\n            <jats:sub>\u03c4<\/jats:sub>\n            ) ratio, did not differ based on renal function. Renal impairment does not alter the propensity for ACV or its metabolites to distribute to the CSF, but the higher concentrations in the systemic circulation, as a result of reduced elimination, are associated with proportionally higher concentrations in CSF.\n          <\/jats:p>","DOI":"10.1128\/aac.00729-09","type":"journal-article","created":{"date-parts":[[2009,12,29]],"date-time":"2009-12-29T01:54:15Z","timestamp":1262051655000},"page":"1146-1151","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":63,"title":["Pharmacokinetics of Acyclovir and Its Metabolites in Cerebrospinal Fluid and Systemic Circulation after Administration of High-Dose Valacyclovir in Subjects with Normal and Impaired Renal Function"],"prefix":"10.1128","volume":"54","author":[{"given":"James P.","family":"Smith","sequence":"first","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Weller","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation, GlaxoSmithKline, Research Triangle Park, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Johnson","sequence":"additional","affiliation":[{"name":"Anesthesiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Nicotera","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Luther","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Haas","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"2680","volume":"18","year":"2003","unstructured":"Almond, M. K. 2003. Aciclovir and valaciclovir neurotoxicity in patients with renal failure. Nephrol. Dial. Transplant.18:2680.","journal-title":"Nephrol. Dial. Transplant."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-005-2808-9"},{"key":"e_1_3_2_4_2","first-page":"1775","volume":"10","year":"1995","unstructured":"de Knegt, R. J., H. van der Pijl, and L. A. van Es. 1995. Acyclovir-associated encephalopathy, lack of relationship between acyclovir levels and symptoms. Nephrol. Dial. Transplant.10:1775-1777.","journal-title":"Nephrol. Dial. 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