In the 5 years since its release for clinical use,
acyclovir (9-[2-hydroxyethoxymethyl]
guanine) has proved to be a safe and effective agent for
therapy of
herpes simplex and
varicella-
zoster infections. The
drug's availability in topical, oral, and intravenous preparations has allowed its use in a range of clinical situations.
Acyclovir must be phosphorylated by viral
thymidine kinase in infected cells, where it then acts to inhibit
viral DNA replication specifically. Epstein-Barr virus and human
cytomegalovirus infections do not seem to respond to
acyclovir therapy, although in-vitro effects on these viruses may be seen.
Acyclovir is well absorbed and distributed, with cerebrospinal fluid levels 50% that of plasma. Clearance is almost entirely by the renal route, with a half-life of 20 hours in the anuric patient.
Acyclovir has an excellent safety profile, its major adverse effect being transient serum
creatinine elevations during high-dose intravenous use. Major uses include treatment of primary and recurrent
genital herpes and
herpes encephalitis and prophyllaxis and
therapy of mucocutaneous herpes and
varicella-
zoster infections in immunocompromised patients. Resistance to
acyclovir in herpes simplex virus is rarely encountered and does not seem to be due to long-term chronic suppressive
therapy.