title: Ganciclovir concentrations in the cerebral extracellular space after valganciclovir treatment; a case study.
abstract: Nearly all glioblastomas (GBMs), brain tumours with very poor prognosis, are infected with human cytomegalovirus (CMV). The anti-CMV drug valganciclovir (VGCV) has shown promise as a treatment option for patients with GBM, but its penetration into the central nervous system (CNS) is unknown. Here we describe a patient with GMB receiving VGCV in whom an intracerebral microdialysis catheter was implanted and ganciclovir (GCV) concentrations in brain extracellular fluid (BECF) and serum were monitored. GCV was rapidly absorbed. Cmax values (at 3 h) in serum and BECF were 19.6 and 10.2 µmol/L, T½ values were 3.2 and 4.5 h, and plasma and BECF AUC0-∞ values were 90.7 and 75.9 µmol h/L, respectively. Thus, VGCV treatment results in significant intracerebral levels of GCV that may be sufficient for therapeutic effects. Further studies of this drug in patients with GBM are warranted.
authors.affiliation: Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden Department of Medicine, Unit for Microbial Pathogenesis, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Inti
authors.initials: I
authors.lastname: Peredo
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Helldén
authors.affiliation: Department of Medicine, Unit for Microbial Pathogenesis, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Wolmer-Solberg
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Pohanka
authors.affiliation: Department of Medicine, Unit for Microbial Pathogenesis, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Stragliotto
authors.affiliation: Department of Medicine, Unit for Microbial Pathogenesis, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Afsar
authors.initials: A
authors.lastname: Rahbar
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Ståhle
authors.affiliation: Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Bo-Michael
authors.initials: BM
authors.lastname: Bellander
authors.affiliation: Department of Medicine, Unit for Microbial Pathogenesis, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Söderberg-Nauclér
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000821:virology; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000378:metabolism; D016903:Drug Monitoring; D005110:Extracellular Space / Q000378:metabolism; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005909:Glioblastoma / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir