Biomedical Engineering Reference
In-Depth Information
24.4.2 CMV I
NHIBITORS
24.4.2.1 Ganciclovir
Structure
(Figure 24.14): 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (DHPG), (GCV), Cymevene
®
,
Cytovene
®
.
Activity spectrum
: HSV (types 1 and 2), CMV, and some other herpesviruses.
Mechanism of action
: Targeted at the viral DNA polymerase, where it mainly acts as a chain ter-
minator, following intracellular phosphorylation to GCV triphosphate and incorporation of GCV
monophosphate at the 3
-end of the viral DNA chain. First phosphorylation step is catalyzed by the
HSV-encoded thymidine kinase (TK) or CMV-encoded protein kinase (PK), which explains the
specii city of ganciclovir for HSV and CMV, respectively.
Principal indication(s)
: CMV infections, particularly CMV retinitis in immunocompromised
(i.e., AIDS) patients (treatment and prevention).
Administered
: Intravenously at 10 mg/kg/day (2 × 5 mg/kg, every 12 h) for induction therapy; orally
at 3000 mg/day (three times four 250 mg capsules) for maintenance therapy and for prevention;
intraocular (intravitreal) implant (Vitrasert*) of 4.5 mg ganciclovir as localized therapy of CMV
retinitis.
′
O
O
N
N
HN
HN
N
N
N
H
2
N
H
2
N
N
O
C
H
2
N
C
O
HO
O
O
CH
H
3
C
CH
3
OH
OH
Ganciclovir
Valganciclovir
NH
2
O
O
3 Na
+
N
-
O
P
C
O
-
O
-
N
O
O
HO
P
O
HO
OH
Foscarnet
Cidofovir
5'-d-[G*C*G*T*T*T*G*C*T*C*T*T*C*T*T*C*T*T*G*C*G]-3'
Sodium salt
* = Racemic phosphorothioate
Fomivirsen
FIGURE 24.14
Structures of a number of cytomegalovirus (CMV) inhibitors.
