Acylete Mechanism of Action

Pharmacology: Pharmacodynamics: Acyclovir is an antiviral agent which is highly active in vitro against herpes simplex virus (HSV) type I and II and varicella zoster virus. Acyclovir is phosphorylated after entry into herpes-infected cells to the active compound acyclovir triphosphate. Acyclovir triphosphate acts as an inhibitor of and substrate for the herpes-specified DNA-polymerase preventing further viral DNA synthesis without affecting normal cellulose processes.
Pharmacokinetics: Acyclovir is only partially absorbed from the gut. It is estimated that 15 ~ 30% of an oral dose of the drug is absorbed. Steady-state peak and trough plasma acyclovir concentrations were not dose proportional over the oral dosing range of 200 ~ 800 mg 6 times daily. Mean steady state peak plasma concentrations following doses of 400 mg administered 4-hourly were 1.21 ug/ml and the equivalent trough plasma levels were 0.63 ug/ml.
Acyclovir is widely distributed into body tissues and fluids including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretions, CSF and herpetic vesicular fluid. The drug is also distributed into semen, achieving concentrations about 1.4 and 4 times those in plasma during chronic oral therapy at dosage of 400 mg and 1 g daily, respectively. Acyclovir crosses the placenta. Limited data indicate that the drug is distributed into milk, generally in concentrations greater than concurrent maternal plasma concentrations, possibly via an active transport mechanism.
From studies with intravenous acyclovir, the terminal plasma half-life has been determined as about 2.9 hours. Most of the drug is excreted unchanged by the kidney. Renal clearance of acyclovir is substantially greater than creatinine clearance indicating that tubular secretion in addition to glomerular filtration contributes to the renal elimination of the drug 9-carboxymethoxymethylguanine is the only significant metabolite of acyclovir and accounts for 10 ~ 15% of the total amount of drug recovered in the urine. In patients with chronic renal failure, the mean terminal half-life was found to be 19.5 hours. The mean acyclovir half-life during haemodialysis was 5.7 hours. Plasma acyclovir levels dropped approximately 60% during dialysis. In the elderly, total body clearance falls with increasing age associated with decreases in creatinine clearance, although there is little change in the terminal plasma half-life.