Preclinical toxicology studies with acyclovir: acute and subchronic tests

Area of Science:

• Pharmacology
• Toxicology
• Drug Safety

Background:

• Acyclovir (ACV) is a novel antiherpes medication.
• Comprehensive toxicity evaluation is crucial for new drug development.

Purpose of the Study:

• To assess the acute and subchronic toxicity of Acyclovir (ACV).
• To determine lethal dose (LD50) values across different administration routes and species.
• To identify potential target organs for ACV toxicity.

Main Methods:

• Acute toxicity tests involving oral, intravenous (IV), and subcutaneous (SC) administration of ACV in mice and rats of various ages.
• Subchronic toxicity studies in mice (1-month oral gavage), rats (3-week IV injection), and dogs (1-month IV injection).
• Observation of clinical signs, mortality, and pathological examination, focusing on renal effects.

Main Results:

• Oral LD50 values for ACV were high (>10,000 mg/kg in mice, >20,000 mg/kg in rats), indicating low oral toxicity.
• IV LD50 values were 405 mg/kg (mice) and >600 mg/kg (rats).
• Obstructive nephropathy was observed in rats receiving rapid IV ACV at 20-80 mg/kg/day, characterized by drug crystal precipitation, but was reversible.
• High IV doses (50-100 mg/kg b.i.d.) were lethal in dogs within 31 days.

Conclusions:

• Acyclovir (ACV) exhibits a favorable acute oral toxicity profile.
• Rapid intravenous administration of ACV can lead to reversible obstructive nephropathy in rats.
• Significant acute toxicity and mortality were observed in dogs following rapid IV administration, highlighting species-specific sensitivity and administration route importance.