Premium
Single‐ and Multiple‐Dose Pharmacokinetics of Levovirin Valinate Hydrochloride (R1518) in Healthy Volunteers
Author(s) -
Huang Yue,
Ostrowitzki Susanne,
Hill George,
Navarro Mercidita,
Berger Nancy,
Kopeck Paul,
Mau Cheng I.,
Alfredson Tom,
Lal Ritu
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005274861
Subject(s) - pharmacokinetics , pharmacology , prodrug , medicine , dosing , oral administration , absorption (acoustics) , urine , volunteer , bioavailability , biology , physics , acoustics , agronomy
R1518 is a valine ester prodrug of levovirin as an investigational new drug for the treatment of hepatitis C virus. Two phase 1, single‐ and multiple‐dose studies were conducted to investigate the pharmacokinetics of R1518 in healthy volunteers. After oral dosing, R1518 was rapidly and exclusively converted to levovirin. Levovirin plasma concentrations peaked at 2 hours, with T 1/2 ranging from 6 to 8 hours. The T 1/2 of R1518 was less than 1 hour, with relative exposures (R1518/levovirin) less than 6%. A high‐fat meal did not affect the pharmacokinetics. The female groups in both studies had higher plasma levels than males did due to age and renal function difference. An accumulation ratio of 1.3 to 1.5 was observed with the twice‐daily regimen. About 75% to 90% of the levovirin equivalent dose was recovered in urine. Increase in exposure was slightly disproportionate to increase in dose. Significantly improved oral absorption of levovirin was achieved following administration of R1518.