title: Sequential treatment of cytomegalovirus infection or disease with a short course of intravenous ganciclovir followed by oral valganciclovir: efficacy, safety, and pharmacokinetics.
abstract: Oral (p.o.) or intravenous (IV) ganciclovir (GCV) has been the first-line agent for prevention and treatment of cytomegalovirus (CMV) infection and disease in solid organ transplantation (SOT). The introduction of p.o. valganciclovir, with higher bioavailability than p.o. GCV, has proven to be a suitable approach toward outpatient p.o. therapy for CMV infection/disease. The present single-arm, exploratory pilot trial performed with 21 patients investigates the efficacy and safety of a short therapeutic course (21 days) based on an initial IV treatment with GCV (5 mg/kg twice daily, for 5 days) followed by p.o. valganciclovir (900 mg twice daily, for 16 days) for CMV infection/disease in SOT patients. In all cases, doses were adjusted for renal function. Moreover, the study allowed comparison of exposure to GCV after p.o. valganciclovir with respect to IV GCV in the same patients. Response to treatment was monitored until day 180. Viral load eradication was achieved in 66.7% of patients, on day 21. Although not statistically significant, a trend was seen toward increased persistence of viral load on day 21 for patients with donor positive/recipient negative CMV serostatus or receiving either anti-rejection therapy or polyclonal anti-thymocyte globulin. CMV clinical infection recurred in 14.3% of patients, with higher recurrence rates in patients with risk factors for persistence of viremia. Exposures to GCV after using IV GCV or p.o. valganciclovir showed comparable values (P=0.054). This short course, combining initial IV GCV and subsequent p.o. valganciclovir, may provide effective exposure and therapeutic response in the treatment of CMV infection in SOT patients with adequate drug exposure and with the additional potential benefit of shortening the length of hospital stay, which may result in cost reduction and improved patient comfort.
authors.affiliation: Nephrology Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Caldés
authors.forename: S
authors.initials: S
authors.lastname: Gil-Vernet
authors.forename: Y
authors.initials: Y
authors.lastname: Armendariz
authors.forename: H
authors.initials: H
authors.lastname: Colom
authors.forename: L
authors.initials: L
authors.lastname: Pou
authors.forename: J
authors.initials: J
authors.lastname: Niubó
authors.forename: L
authors.initials: L
authors.lastname: Lladó
authors.forename: J
authors.initials: J
authors.lastname: Torras
authors.forename: N
authors.initials: N
authors.lastname: Manito
authors.forename: G
authors.initials: G
authors.lastname: Rufí
authors.forename: J M
authors.initials: JM
authors.lastname: Grinyó
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir