Efficacy and pharmacokinetics of adefovir dipivoxil liquid suspension in patients with chronic hepatitis B and renal impairment.
The study evaluated whether a liquid suspension of adefovir dipivoxil (ADV) is effective and safe when dose adjusted based on varying degrees of renal impairment in patients with chronic hepatitis B. Patients had stable mild, moderate, or severe renal impairment or end-stage renal disease. Twenty-eight patients were enrolled: 10 (mild), 12 (moderate), and 6 severe renal impairment or end-stage renal disease with hemodialysis. Statistical testing demonstrated that daily dosages of ADV liquid suspension at 10 mg and 5 mg in the mild and moderate renal impairment groups, respectively, were clinically similar to ADV 10-mg tablets. However, the antiviral effect observed with the 5-mg/d dose was clearly numerically less than that observed with the 10-mg/d dose. Steady-state adefovir plasma exposures after administration of the ADV liquid suspension were generally within the ranges observed in patients with normal renal function. Treatment with ADV liquid suspension for up to 48 weeks was generally well tolerated. The daily dose-adjustment approach was not clearly safer or more efficacious than the dosing-interval adjustment. Therefore, the results do not support daily ADV dosing using a liquid suspension over the current strategy of adjustment of the ADV dosing interval in patients with impaired renal function.
Shiffman
Mitchell L
ML
Virginia Commonwealth University Medical Center, Richmond, Virginia, USA. mitchell_shiffman@bshsi.org
Pol
Stanislas
S
Rostaing
Lionel
L
Schiff
Eugene
E
Thabut
Dominique
D
Zeuzem
Stefan
S
Zong
Jian
J
Frederick
David
D
Rousseau
Franck
F
D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019999:Pharmaceutical Solutions / Q000493:pharmacokinetics / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000097:blood* / Q000188:drug therapy; D016896:Treatment Outcome
D000998:Antiviral Agents; D063065:Organophosphonates; D019999:Pharmaceutical Solutions; D000225:Adenine; C106812:adefovir dipivoxil