Sahin S.Ates M.2024-08-042024-08-04202397988911335639798891133013https://hdl.handle.net/11616/92344Acyclovir (2-amino-9-(2-hydroxyethoxymethyl)-1H-purin-6-one) is an antiviral drug that is a guanine nucleoside analogue. The molecule was discovered in 1974. Clinical trials started in 1977, and it was marketed for the first time in 1981. Since then, acyclovir has become one of the most used antiviral drugs worldwide. It was included in the WHO Model List of Essential Medicines in October 2013. It is used in the treatment of herpes simplex viruses, varicella-zoster virus, Epstein-Barr virus and cytomegalovirus. After acyclovir uptake, it is converted to acyclovir monophosphate by thymidine kinase. Since this transformation occurs in infected cells, the specificity of drug increases. Cellular enzymes convert the acyclovir monophosphate to acyclovir triphosphate. Acyclovir triphosphate inhibits DNA polymerase, inhibiting DNA synthesis and viral replication. Acyclovir is commercially available as tablets (200 mg, 400 mg, and 800 mg), oral suspension (400 mg/5 mL), topical cream (5%), intravenous injection (25 mg/mL, sodium salt), and ophthalmic ointment (3%). Acyclovir is slightly soluble in water (1.2-1.6 mg/mL at 22-25°C) and its solubility affected by pH (2.3 mg/mL at pH 5.8). Although aqueous solubility of acyclovir is more than 100 mg/mL at 25°C, it is nonionic at pH 7.4 (maximum solubility 2.5 mg/mL at 37°C). Acyclovir is an amphoteric molecule with two pKa values (2.27 and 9.25). Acyclovir is classified as Class III (high solubility, low permeability/poor metabolism) drug according to Biopharmaceutics Classification System (BCS), and Class IV for the Biopharmaceutics Drug Disposition Classification System (BDDCS). Absorption of acyclovir is slow, variable and insufficient, and its oral bioavailability is low (10-30%). Maximum plasma concentration is reached within 1.5-2.5 hours. After multiple dosing, steady-state concentration is reached within 1-2 days. Acyclovir is widely distributed in many body tissues including lung, brain, kidney, spleen, heart, liver, muscle, placenta and uterus. The protein binding of acyclovir is 9-33% and the volume of distribution is 48 L/1.73 m2. The main route of elimination is renal excretion as unchanged drug via glomerular filtration and tubular secretion. Acyclovir is metabolized in the liver (8-14%) and converted to its pharmacologically inactive metabolite 9-(carboxymethoxy)methyl] guanine. The half-life is about 2.5 hours. Acyclovir is well tolerated, but some adverse effects such as nausea, vomiting, diarrhea, and headache may occur depending on the route of administration. In addition, skin rash and contact dermatitis can be seen in topical applications. Intravenous infusion may cause nephropathy and phlebitis due to crystallization in the renal tubules. Acute renal failure can develop very rarely. In this chapter, physicochemical and pharmacokinetic properties of acyclovir will be given in detail. © 2024 Nova Science Publishers, Inc.eninfo:eu-repo/semantics/closedAccessAcyclovirPharmacokinetic propertiesPharmacological propertiesPhysicochemical characteristicsBook Chapter43852-s2.0-85182619548N/A