title: Pharmacokinetic comparison of the maleate and free base formulations of LB80380, a novel nucleotide analog, in healthy male volunteers.
abstract: OBJECTIVE
  LB80380, a dipivoxil ester prodrug of LB80331, is a novel antiviral agent for the treatment of chronic hepatitis B. The aim of this study was to compare the pharmacokinetic differences after single oral administrations of the free base and maleate formulations of LB80380 in healthy male subjects.
  
  
  METHODS
  An open-label, single- dose, randomized-sequence, 2-treatment crossover study was conducted in 32 Korean male volunteers. Subjects received either a combination of 60 and 90 mg tablets of the free base LB80380 formulation or a 183 mg (150 mg as a free base) tablet of the maleate LB80380 formulation. Then, after a 14- day washout period, each subject received the other formulation. Plasma and urine concentrations of LB80331 and LB80317 (active metabolites of LB80380) were measured by validated liquid chromatographytandem mass spectrometry assays. A safety assessment, which included vital signs, adverse events, electrocardiograms and clinical laboratory tests, was performed for each subject.
  
  
  RESULTS
  A total of 32 healthy subjects was enrolled, and 26 subjects completed the study. Single oral administrations of LB80380 maleate tablets did not result in clinically significant differences in the safety profile compared to the LB80380 free base tablets. The 90% confidence intervals (CIs) for the geometric mean ratios of Cmax and AUClast for LB80331 of the two treatments (maleate versus free base formulation) were 0.986 - 1.1240 and 0.9848 - 1.0533, respectively. The 90% CIs for the geometric mean ratios of Cmax and AUClast for LB80317 were 0.8379 - 0.9696 and 0.7224 - 0.9196.
  
  
  CONCLUSIONS
  In healthy male subjects, the 183 mg LB80380 maleate tablet was pharmacokinetically equivalent to the 60 and 90 mg LB80380 free base tablets.
authors.affiliation: Clinical Trial Center Samsug Medical Center, Seoul, South Korea.
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Jung
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Kim
authors.forename: Tae-Eun
authors.initials: TE
authors.lastname: Kim
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Ko
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008298:Maleates / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D056910:Republic of Korea; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: C487369:((1-((2-amino-9H-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonic acid dipivoxyl; D000998:Antiviral Agents; D008298:Maleates; D063065:Organophosphonates; D011355:Prodrugs; D013607:Tablets; D006147:Guanine