ME/CFS Research :: Antivirals

Antiviral Pharmacokinetic Information

The following information on antivirals might be useful.

Epstein-Barr Virus

• acyclovir (metabolite of valacyclovir/Valtrex)
  • EBV IC50: median 7.0μM (1.58μg/mL*), max: 10μM (2.25μg/mL*)
    • 4.1 μM (Meng 2010)
    • 6.0 μM (Colby 1980)
    • 8.6 μM (Drosu 2020)
    • 10.0 μM (Zacny 1999)
  • Pharmacokinetics of 1,000mg valacyclovir
    
    • Acyclovir Cmax: 5.65 μg/mL ± 2.37 (when given once daily) or 4.96 μg/mL ± 0.64 (when given 4x/day)
    • Cmax is 220% of the IC50max for EBV
    • Elimination half-life: 2.91 hr ± 0.63 (young) or 3.11 ± 0.51 (elderly) (healthy volunteers with normal renal function)
    • est. 1g 4x daily Cavg = Cmax*0.53† = 2.63 μg/mL; this is 116.8% of the IC50max
    • est. 1g 4x daily Cmin = Cmax*0.24† = 1.19 μg/mL; this is 52.8% of the IC50max
  • *μM to μg/mL conversion factor: 4.44 μM = 1 μg/mL (source: ChatGPT and Van der Meulen 2006)
  • †Indicates AI assisted calculation
• ganciclovir (metabolite of valganciclovir/Valcyte)
  • EBV IC50: median 0.78μM (0.20μg/mL*), max 1.50μM (0.38μg/mL*)
    • 0.05μM (Lin 1983)
    • 1.50μM (Meng 2010)
    • 0.65μM (Drosu 2020)
  • Pharmacokinetics of 900mg valganciclovir once daily with food: (ref. Package insert)
    
    • Ganciclovir Cmax: 5.61 μg/mL ± 1.52
    • Cmax is 1475% of the IC50max for EBV
    • Elimination half-life: 4.08 hr ± 0.76
    • est. Cavg = Cmax*0.240† = 1.35 μg/mL; this is 355% of the IC50max
    • est. Cmin = Cmax*0.016† = 0.09 μg/mL; this is 6% of the IC50max
  • Compared to acyclovir, the viral inhibitory effect persists longer after drug removal (Lin 1983)
  • Ganciclovir is associated with liver toxicity and liver cancer which limits the dosage and treatment duration
  • *μM to μg/mL conversion factor: 3.99 μM = 1 μg/mL (source: Package insert)
  • †Indicates AI assisted calculation
• spironolactone
  • EBV IC50: 2.1μM (Verma 2016) (38% lower than acyclovir in the same assay)
  • Pharmacokinetics: Cmax of 100mg spironolactone given for 15 days was 80g/mL (Gardiner 1989)
  • Uniquely inhibits SM protein function, in contrast to acyclovir and ganciclovir, which inhibit EBV DNA polymease; SM protein is used in several steps of the replication process; resistance to inhibitors of DNA polymerase is unlikely to lead to spironolactone cross-resistance (Verma 2016)
• tenofovir alafenamide (Vemlidy)
  • EBV IC50: 0.084μM (0.040 μg/mL, ChatGPT conversion) (Drosu 2020)
  • Cmax = 0.27μg/mL
  • Cmax is 675% of the IC50 for EBV
  • Compared to acyclovir, the viral inhibitory effect persists longer after drug removal (Drosu 2020)