Covir 800 Mechanism of Action

Pharmacology: Pharmacodynamics: Aciclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus type 1 (HSV-1), 2 (HSV-2), and Varicella Zoster Virus (VZV). In cell culture, aciclovir's highest antiviral activity is against HSV-1, followed in decreasing order of potency against HSV-2 and VZV.
The inhibitory activity of aciclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts aciclovir into aciclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In accomplished in 3 ways: competitive inhibition of viral DNA polymerase; incorporation into and termination of the growing viral DNA chain; and inactivation of the viral DNA polymerase. The greater antiviral activity of aciclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral TK.
Pharmacokinetics: Absorption: Absorption of aciclovir from the GI tract is variable and incomplete. It is estimate that 10-30% of an oral dose of the drug is absorbed. Some data suggest that GI absorption of aciclovir maybe saturable; in a crossover study in which aciclovir was administered orally to healthy adults as 200-mg capsules, 400-mg tablets, or 800-mg tablets 6 times daily, the extent of absorption decreased with increasing dose, resulting in bioavailabilities of 20, 15, or 10%, respectively. It is stated that this decrease in bioavailability appears to be a function of increasing dose, not differences in dosage forms. In addition, steady-state peak and through plasma aciclovir concentrations were not dose proportional over the oral dosing range of 200-800 mg 6 times daily, averaging 0.83 and 0.46, 1.21 and 0.63, or 1.61 and 0.83 mcg/mL for the 200-, 400-, or 800-mg dosing regimens, respectively. Peak plasma concentrations of aciclovir usually occur within 1.5-2.5 hours after oral administration. Food does not appear to affect absorption of aciclovir.
Distribution: Aciclovir is widely distributed into body tissues and fluids including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretion, CSF, and herpetic vesicular fluid.
The apparent volume of distribution of aciclovir: Adults: 32.4-61.8 L/1.73 m².
Children 7-12 years: 51.2-53.6 L/1.73 m².
Children 2-7 years: 42 L/1.73 m².
Children 1-2 years: 31.6 L/1.73 m².
Neonates up to 3 months of age: 28.8 L/1.73 m².
Aciclovir is approximately 9-33% bound to plasma proteins at plasma concentration of 0.41-5.2 mcg/mL.
Elimination: Plasma concentrations of aciclovir appear to decline in a biphasic manner. In adults with normal renal function, the half-life of aciclovir in the initial phase averages 0.34 hours and the half-life in the terminal phase averages 2.1-3.5 hours. In adults with renal impairment, both phases may be prolonged, depending on the degree of renal impairment. Aciclovir is excreted principally in urine via glomerular filtration and tubular secretion. The only known urinary metabolite is 9-carboxymethoxymethylguanine. Aciclovir is removed by hemodialysis.