Pharmacokinetics and Pharmacodynamics of Sofosbuvir in Adults and Special Populations: A Systematic Review

Hepatitis C virus (HCV) infection affects more than 70 million individuals globally and remains a leading cause of cirrhosis, hepatocellular carcinoma, and liver-related mortality. The advent of direct-acting antivirals (DAAs) has transformed therapy, with sofosbuvir, a uridine nucleotide prodrug, serving as a cornerstone of modern regimens. Following oral absorption, sofosbuvir undergoes hepatic activation to the active triphosphate metabolite GS-461203, which inhibits the NS5B RNA-dependent RNA polymerase, resulting in termination of viral RNA synthesis. The major circulating metabolite GS-331007, primarily renally excreted, accounts for most systemic exposure. Sofosbuvir exhibits rapid absorption (T_max 0.5–2 h), moderate plasma protein binding (61–65%), and elimination predominantly via the kidneys (~80% of dose), with half-lives of ~0.4 h (parent drug) and ~27 h (GS-331007). Pharmacokinetic studies show that renal impairment significantly increases GS-331007 exposure, particularly in dialysis patients, though sustained virologic response (SVR) rates remain high with careful monitoring. In contrast, hepatic impairment, advanced age, and HIV coinfection exert minimal effects on exposure, and dose adjustment is generally unnecessary. Sofosbuvir-based regimens are approved for adults, children ≥3 years, and are widely used in transplant settings, though pregnancy data remain limited. The drug is well tolerated, with headache, fatigue, and nausea being the most common adverse effects, while serious risks include HBV reactivation and rare bradycardia with amiodarone.