VALGANCYCLOVIR
MOA
- Diastomers are rapidly
hydrolyzed to ganciclovir
- Initial phosphorylation is
activated by protein-kinase
phosphotransferase in CMV
- Inhibition of DNA polymerase
- Termination of viral DNA
elongation
MOA
- Nucleoside analog
- Requires 3 phosphorylation
steps for activation
- Fist involves viral thymidine
kinas
- Acyclovir triphosphate inhibits
viral DNA synthesis
MOA
- Fluorinated pyrimidine
nucleoside
- Phosphorylated intracellularly
by host cell enzymes
- Competes with thymidine
triphosphate for incorporation
(viral DNA polymerase)
- Incorporation of trifluridine
triphosphate into both viral and
host DNA
USES PHARMACOKINETICS DOSAGE
- CMV Infections ¬ Absorption: Well
- Retinitis, Patients with AIDS absorbed from the GI
- Prophylaxis, tract. Increased
Immunocompromised absorption if taken w/
- Colitis food. Bioavailability:
- HIV patients Approx 60%.
¬ Peak plasma
- Kidney tranplantat
concentration: 1-3 hr.
- Kidney-pancreas transplant
¬ Distribution: Widely
- Heart transplant distributed to all tissue
including CSF and
ocular tissue.
¬ Metabolism:
Converted to
ganciclovir by rapid
first-pass intestinal or
hepatic metabolism
¬ Excretion: via urine as
gancyclovir
ACYCLOVIR
USES PHARMACOKINETICS
- Clinical activity against HSV-1, ¬ Absorption: 15-30%
HSV-2, and VZV, but it is from GI
approximately 10 times more ¬ Not affected by food
potent against HSV-1 and HSV-2 ¬ Can achieve
than against VZV therapeutic serum
- In vitro activity against Epstein- levels
Barr virus (EBV), ¬ Disttribution: Peak at
cytomegalovirus (CMV), and 1.5-2 hours
human herpesvirus-6 (HHV-6) is ¬ Half life of 3 hours
present but weaker. ¬ Metabolism: Liver
- Intravenous acyclovir- treatment ¬ Elimination: Kidneys
of choice for herpes simplex
encephalitis, neonatal HSV
infection, and serious HSV or
VZV infections.
TRIFLURIDINE
USES PHARMACOKINETICS
Primary keratoconjunctivitis and ¬ Absortion: Absorbed
recurrent epithelial keartitis due to through he cornea wih
HSV increased penetration in
the presence of epithelial
defect or inflammation
¬ Distribution: Onset: 2-7
days
¬ Elimination: Half life: 12
minutes
SIDE EFFECTS CONTRAINDICATIONS
900 mg Abdominal pain hypersentivity
Retinitis: BID for 21 days Graft rejection
Retinitis Maintenace: Once Neuropathy
daily Headache
Prophylaxis: Once daily for 10- Nausea
100 days
Kidney transplant: once daily
for 200 days
DOSAGE SIDE EFFECTS CONTRAINDICATIONS
400 mg: Primary infection Nausea Hypersentivity
(TID 7-10 days) Diarrhea
800 mg Headache
Recurrent genital herpes: TID Neurologic effects
2 days, BID 5 days Renal toxicity
VZV: Oral beigin 24h, onset of
rash, QID 5 dyas
HZV: Begin with 72 h, 5
times/day 7 days
DOSAGE (IV):
5 mg/kg: every 8h for 7-14
dyas
10 mg/kg: <1 yea old, every 8h
or 7 to 10 days or until no
lesions or 48 h
10-20 mg/kg: 1 to 12 years old,
every 8hfor 7-10 days or untiil
no new lesions for 48h
DOSAGE SIDE EFFECTS CONTRAINDICATIONS
1% solution: 1 drop in affected Corneal irritation Hypersenvity
eye every 2 hours (max: 9 Epithelial keratopathy
drops daily; min of 5 drops) Increased intraocular
until complete re- pressure
epithelization. Reduce to 1
drop every 4 hours for 7 days.
Maximum of 21 days.