CNS 18 - 9 
3.0 DRUG, VECTOR, GENE, PRODUCER CELL LINE INFORMATION 
3.1 Ganciclovir (GCV, Cytovene) 
Source: Commercially available (Syntex corporation, Palo Alto, CA) 
Pharmacology: Ganciclovir is a synthetic nucleoside analogue of 
2’deoxyguanosine that inhibits replication of herpesviruses both in vitro and in 
vivo. Sensitive human viruses include cytomegalovirus, herpes simples virus types 
1 and 2, varicella zoster virus. Evidence indicates that upon entry into host cells, 
these viruses induce cellular kinases that phosphorylate ganciclovir to its 
triphosphate. Ganciclovir is believed to inhibit viral DNA synthesis by direct 
competitive inhibition of viral DNA polymerases and direct incorporation into 
viral DNA resulting in eventual termination of DNA chain elongation. 
GCV does cross the blood-brain-barrier. The cerebrospinal fluid to plasma ratio 
is from 0.24 to 0.70 (0.31-0.68 ug/ml in CSF and 0.44-2.2 ug/ml in plasma). 
The above CSF and plasma concentrations are expected to be within the range of 
GCV needed to kill the HS-tk transduced cells based on in vitro and pre-clinical 
in vivo studies (0.5 ug/ml will prevent growth of HS-tk transduced tumor cells). 
Formulation and Stability and Route of Administration: Sterile powder is 
supplied in 10 ml vials, each containing ganciclovir sodium equivalent to 500 mg 
of ganciclovir. Vials may be stored at room temperature, and the drug is stable 
at temperatures less than 40° C. Ganciclovir is reconstituted with 10 ml of sterile 
water for injection. This results in a solution of 50 mg/ml ganciclovir. Note: Do 
not use bacteriostatic water containing parabens for iryection. It is 
incompatible and may lead to drug precipitation. The reconstituted drug is 
stable at room temperature for 12 hours, after which it must be discarded. It 
should not be kept refrigerated. Prior to administration, the appropriate amount 
of drug should be further diluted with 0.9% saline to a final concentration of 10 
mg/ml or less. Ganciclovir is to be infused intravenously over 1 hour. Do not 
give as a rapid or bolus administration. Because non-bacteriostatic saline is used 
for reconstitution, ganciclovir should be used promptly after reconstitution. 
Solutions greater than 12 hours old should be discarded. 
Toxicity: Hematologic toxicity, dominantly thrombocytopenia and 
granulocytopenia have been seen with a frequency of up to 32% in 
immunosuppressed patients with AIDs, transplant recipients, or patients with bone 
marrow allografts. In non-immunosuppressed patients the frequency of such 
events is not greater than that associated with placebo. Hematologic toxicity 
appears transient and generally responds to withdrawal of ganciclovir. Renal 
toxicity, consisting of transient and reversible increases in serum creatinine to 
greater than 2.5 mg/dl may occur in up to 18% of patients during drug 
administration, and may require dose modification. Transient complaints of 
headache and confusion may also occur. 
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Recombinant DNA Research, Volume 18 
