Plasma and CSF pharmacokinetics of ganciclovir in nonhuman primates

Baruti M. Serabe, Daryl J. Murry, Robert Dauser, Jed Nuchtern, John Durfee, Leticia McGuffey, Stacey Berg, Susan M. Blaney

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Purpose: The antiviral nucleoside analogue ganciclovir is a potent inhibitor of replication in herpes viruses and is effective against cytomegalovirus infections in immunocompromised patients. Ganciclovir is also used in cancer gene therapy studies that utilize the herpes simplex virus thymidine kinase gene (HSV-TK). The pharmacokinetics of ganciclovir in adults and children have been described previously but there are no detailed studies of the CNS pharmacology of ganciclovir. We studied the pharmacokinetics of ganciclovir in plasma and CSF in a nonhuman primate model that is highly predictive of the CSF penetration of drugs in humans. Methods: Ganciclovir, 10 mg/kg i.v., was administered over 30 min to three animals. Ganciclovir concentrations in plasma and CSF were measured using reverse-phase HPLC. Results: Peak plasma ganciclovir concentrations ranged from 18.3 to 20.0 μg/ml and the mean plasma AUC was 1075 ± 202 μg/ml · min. Disappearance of ganciclovir from the plasma was biexponential with a distribution half- life (t(1/2)α) of 18 ± 7 min and an elimination half-life (t(1/2)β) of 109 ± 7 min. Total body clearance (Cl(TB)) was 9.4 ± 1.6 ml/min/kg. The mean CSF ganciclovir AUC was 168 ± 83 μg/ml · min and the mean peak CSF concentration was 0.7 ± 0.3 μg/ml. The ratio of the AUCs in CSF and plasma was 15.5 ± 7.1%. Conclusions: Ganciclovir penetrates into the CSF following i.v. administration. This finding will be useful in the design of gene therapy trials involving the HSV-TK gene followed by treatment with ganciclovir in CNS or leptomeningeal tumors.

Original languageEnglish (US)
Pages (from-to)415-418
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume43
Issue number5
DOIs
StatePublished - Mar 18 1999

Fingerprint

Ganciclovir
Pharmacokinetics
Primates
Plasmas
Viruses
Area Under Curve
Gene therapy
Thymidine Kinase
Genes
Simplexvirus
Genetic Therapy
Half-Life
Neoplasm Genes
Cytomegalovirus Infections
Immunocompromised Host
Nucleosides
Antiviral Agents
Tumors
Animals
High Pressure Liquid Chromatography

Keywords

  • CSF
  • Ganciclovir
  • Nonhuman primates
  • Pharmacokinetics
  • Plasma

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Serabe, B. M., Murry, D. J., Dauser, R., Nuchtern, J., Durfee, J., McGuffey, L., ... Blaney, S. M. (1999). Plasma and CSF pharmacokinetics of ganciclovir in nonhuman primates. Cancer Chemotherapy and Pharmacology, 43(5), 415-418. https://doi.org/10.1007/s002800050916

Plasma and CSF pharmacokinetics of ganciclovir in nonhuman primates. / Serabe, Baruti M.; Murry, Daryl J.; Dauser, Robert; Nuchtern, Jed; Durfee, John; McGuffey, Leticia; Berg, Stacey; Blaney, Susan M.

In: Cancer Chemotherapy and Pharmacology, Vol. 43, No. 5, 18.03.1999, p. 415-418.

Research output: Contribution to journalArticle

Serabe, BM, Murry, DJ, Dauser, R, Nuchtern, J, Durfee, J, McGuffey, L, Berg, S & Blaney, SM 1999, 'Plasma and CSF pharmacokinetics of ganciclovir in nonhuman primates', Cancer Chemotherapy and Pharmacology, vol. 43, no. 5, pp. 415-418. https://doi.org/10.1007/s002800050916
Serabe, Baruti M. ; Murry, Daryl J. ; Dauser, Robert ; Nuchtern, Jed ; Durfee, John ; McGuffey, Leticia ; Berg, Stacey ; Blaney, Susan M. / Plasma and CSF pharmacokinetics of ganciclovir in nonhuman primates. In: Cancer Chemotherapy and Pharmacology. 1999 ; Vol. 43, No. 5. pp. 415-418.
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