Ganciclovir oral bioavailability

Oral and parenteral do.sagc forms of ganciclovir are available. but oral bioavailability is poor. Only 5 to IO r of an oral dose is absorbed. Intravenous administration is preferable. More than 90% of the unchanged drug is excreted in the urine. Ganciclovir for injection is available as a lyophili/ed sodium salt for reconstitution in normal saline. S% dextrose in water, or lactated Ringer s solution. These. solutions are stningly alkaline (pH 11) and must be administered by slow, constant, intravenous infusion to avoid thrombophlebitis. 

Pharmacokinetics Ganciclovir is usually given intravenously and penetrates well into tissues, including the eye and the CNS. The drug undergoes renal elimination in direct proportion to creatinine clearance. Although oral bioavailability is less than 10%, an oral formulation is available for maintenance therapy. 

Penciclovir (Fig. 23.17) is closely related to ganciclovir in structure and has the same mechanism of action. Penciclovir has similar activity to aciclovir against herpes simplex infection. Its safety is similar to that of aciclovir due to its lack of effect on DNA synthesis in uninfected cells. A closer structural similarity to deoxyguanosine makes penciclovir a superior substrate in comparison to aciclovir for viral thymidine kinase, resulting in an enhancement of phosphorylation. This is offset by reduced activity of penciclovir triphosphate as an inhibitor of DNA synthesis. It has poor oral bioavailability and is used in the form of a cream (1% w/w) to treat labial herpes. Famciclovir (Fig. 23.17) is a prodmg of penciclovir which has good oral bioavailability (73%) and is deacetylated and oxidised (aldehyde oxidase) in the liver to penciclovir. The toxicity of famciclovir is low. It is administered three times a day by mouth, whereas treatment of herpes with aciclovir by the oral route requires five daily doses. 

Absorption - Absolute bioavailability of oral ganciclovir under fasting conditions was approximately 5% following food it was 6% to 9%. When given with a high-fat meal, steady-state AUC increased and there was a significant... 

Ganciclovir may be administered intravenously, orally, or via intraocular implant. The bioavailability of oral ganciclovir is poor. Cerebrospinal fluid concentrations are approximately 50% of those in serum. The elimination half-life is 4 hours, and the intracellular half-life is prolonged at 16-24 hours. Clearance of the drug is linearly related to creatinine clearance. Ganciclovir is readily cleared by hemodialysis. 

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