伐昔洛韦, Valaciclovir

Valacyclovir is an antiviral drug used in the management of herpes simplex, herpes zoster, and herpes B.IC50 Value: 2.9 microg/ml (for HSV-1 W)[4].Target: HSV infectionin vitro: VACV uptake was concentration dependent and saturable with a Michaelis-Menten constant and maximum velocity of 1.64 +/- 0.06 mM and 23.34 +/- 0.36 nmol/mg protein/5 min, respectively. A very similar Km value was obtained in hPEPT1/CHO cells and in rat and rabbit tissues and Caco-2 cells, suggesting that hPEPT1 dominates the intestinal transport properties of VACV in vitro [5].in vivo: For treatment of a first episode of genital herpes, a large comparative trial has shown that valacyclovir (1 g twice a day) is as effective as acyclovir (200 mg five times a day) when given for 10 days. For treating recurrences, two trials show that valacyclovir is as effective as acyclovir (200 mg five times a day) with a treatment period of 5 days. A daily dose of 1 g of valacyclovir is as effective as 2 g daily. Valacyclovir can be administered once a day[1]. The concentrations of acyclovir in serum and CSF were measured at steady state after 6 days of oral treatment with 1,000 mg of valacyclovir three times a day [2]. EC50 values of PE and AC in 3T3 cells were 0.02 and 0.01 ug/ml, while values in BHK cells were 0.2 and 0.03 ug/ml. Treatment of infected immunosuppressed mice and FA and VA (b.i.d., 5.5 days) reduced the proportion with erythema from 100% to 24% and 38%, and eliminated ear paralysis, ear lesions (vesicles, etc) and death. Virus was absent from ear and brainstem by day 6, but reappeared after discontinuation in mice treated with VA [3].Clinical trial: Evaluation of Valaciclovir in Patients with Chickenpox. 

Title: Valacyclovir

CAS Registry Number: 124832-26-4

CAS Name: L-Valine 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester

Additional Names: L-valine ester with 9-[(2-hydroxyethoxy)methyl]guanine; valaciclovir; ValACV

Molecular Formula: C13H20N6O4

Molecular Weight: 324.34

Percent Composition: C 48.14%, H 6.22%, N 25.91%, O 19.73%

Literature References: L-Valine ester prodrug of acyclovir, q.v. Prepn: T. A. Krenitsky et al., EP 308065; L. M. Beauchamp, US 4957924 (1989, 1990 both to Wellcome). Evaluation as prodrug: L. M. Beauchamp et al., Antiviral Chem. Chemother. 3, 157 (1992). Clinical pharmacokinetics: S. Weller et al., Clin. Pharmacol. Ther. 54, 595 (1993). Review of pharmacology and clinical efficacy in herpes virus infections: C. M. Perry, D. Faulds, Drugs 52, 754-772 (1996). Clinical trial to prevent cytomegalovirus disease in renal transplantation: D. Lowance et al., N. Engl. J. Med. 340, 1462 (1999); to prevent transmission of genital herpes: L. Corey et al., ibid. 350, 11 (2004).

Derivative Type: Hydrochloride

CAS Registry Number: 124832-27-5

Manufacturers' Codes: 256U; BW-256U87; BW-256

Trademarks: Valtrex (GSK)

Properties: Crystalline solid, occurs as hydrate. uv max (water): 252.8 nm (e 8530). Soly in water: 174 mg/ml.

Absorption maximum: uv max (water): 252.8 nm (e 8530)

Therap-Cat: Antiviral.

Keywords: Antiviral; Purines/Pyrimidinones.