title: Comparison of the pharmacokinetics, safety, and tolerability of vitamin D3 in DP-R206 (150-mg ibandronate/24,000-IU vitamin D3 tablet) and as monotherapy (24,000 iu) in healthy male Korean adults.
abstract: BACKGROUND
  Combined treatment with a bisphosphonate and vitamin D has been proposed for postmenopausal osteoporosis. A new, fixed-dose combination tablet of ibandronate plus vitamin D3 has been developed for monthly administration to treat postmenopausal osteoporosis.
  
  
  OBJECTIVE
  The main objective of the present study was to compare the pharmacokinetics of vitamin D3 administered in 2 forms: a newly developed ibandronate 150-mg/vitamin D3 24,000-IU tablet (DP-R206, test drug) and a stand-alone vitamin D3 24,000-IU tablet (reference drug). A secondary objective was to evaluate the safety and tolerability of DP-R206 in healthy adult male Korean volunteers.
  
  
  METHODS
  This study was a single-dose, open-label, randomized-sequence, 2-treatment, 2-way crossover trial. Blood samples were collected from 24 hours' predose to 120 hours' postdose. The plasma concentrations of vitamin D3 were analyzed by using a validated HPLC-MS/MS method. Pharmacokinetic parameters were calculated, and the 90% CIs of the ratios of the geometric means of the parameters were determined from the logarithmically transformed data by using ANOVA.
  
  
  RESULTS
  Thirty-sex healthy adult male Korean volunteers with a mean (SD) age of 25.8 (2.7) years, a mean height of 174.0 (5.9) cm, and a mean weight of 69.1 (6.2) kg were enrolled; 29 participants completed the study. The 90% CIs of the ratios of the geometric means (test drug/reference drug) of the baseline-corrected Cmax, AUC0-last, and AUC0-∞ values were 0.93 to 1.24, 0.89 to 1.19, and 0.87 to 1.18, respectively. The 90% CIs of the ratios of the geometric means (test drug/reference drug) of the baseline-uncorrected Cmax, AUC0-last, and AUC0-∞ values were 0.93 to 1.24, 0.88 to 1.19, and 0.87 to 1.18, respectively. Eighty-four adverse events (AEs) were reported in 24 of 32 subjects receiving DP-R206, and 14 AEs were reported in 8 of 29 subjects receiving the vitamin D3 24,000-IU tablet. All of the subjects who experienced AEs recovered without sequelae, and no serious AEs were observed.
  
  
  CONCLUSIONS
  The vitamin D3 pharmacokinetics were similar for DP-R206 and the 24,000-IU vitamin D3 tablet. DP-R206 was well tolerated.
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Jeon
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; Department of Radiation Oncology, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Im
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Yunjeong
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; Department of Endocrinology and Metabolism, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Park
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Soo-Wan
authors.initials: SW
authors.lastname: Chae
authors.affiliation: Research and Development Center, DreamPharma Corp, Seoul, Republic of Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Research and Development Center, DreamPharma Corp, Seoul, Republic of Korea.
authors.forename: Hun
authors.initials: H
authors.lastname: Jun
authors.affiliation: Research and Development Center, DreamPharma Corp, Seoul, Republic of Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. Electronic address: mgkim@jbnu.ac.kr.
authors.forename: Min-Gul
authors.initials: MG
authors.lastname: Kim
mesh_terms: D000328:Adult; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002762:Cholecalciferol / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004338:Drug Combinations; D006801:Humans; D000077557:Ibandronic Acid; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; C000592733:DP-R206; D004164:Diphosphonates; D004338:Drug Combinations; D013607:Tablets; D002762:Cholecalciferol; D000077557:Ibandronic Acid
keywords: ibandronate; osteoporosis; pharmacokinetics; vitamin D(3)