PMID- 24378207 OWN - NLM STAT- MEDLINE DCOM- 20141104 LR - 20181203 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 36 IP - 1 DP - 2014 Jan 1 TI - 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. PG - 48-57 LID - S0149-2918(13)01109-0 [pii] LID - 10.1016/j.clinthera.2013.12.001 [doi] AB - 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. OBJECTIVES: 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-infinity 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-infinity 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. CI - (c) 2014 Elsevier HS Journals, Inc. All rights reserved. FAU - Jeon, Ji-Young AU - Jeon JY AD - Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. FAU - Lee, Sun Young AU - Lee SY AD - 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. FAU - Im, Yong-Jin AU - Im YJ AD - Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. FAU - Kim, Eun-Young AU - Kim EY AD - Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. FAU - Kim, Yunjeong AU - Kim Y AD - Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. FAU - Park, Tae Sun AU - Park TS AD - 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. FAU - Chae, Soo-Wan AU - Chae SW AD - Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. FAU - Lee, Jae Won AU - Lee JW AD - Research and Development Center, DreamPharma Corp, Seoul, Republic of Korea. FAU - Jun, Hun AU - Jun H AD - Research and Development Center, DreamPharma Corp, Seoul, Republic of Korea. FAU - Lee, Tae Won AU - Lee TW AD - Research and Development Center, DreamPharma Corp, Seoul, Republic of Korea. FAU - Kim, Min-Gul AU - Kim MG AD - Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. Electronic address: mgkim@jbnu.ac.kr. LA - eng SI - ClinicalTrials.gov/NCT01577849 PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20131228 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Bone Density Conservation Agents) RN - 0 (DP-R206) RN - 0 (Diphosphonates) RN - 0 (Drug Combinations) RN - 0 (Tablets) RN - 1C6V77QF41 (Cholecalciferol) RN - UMD7G2653W (Ibandronic Acid) SB - IM EIN - Clin Ther. 2014 Mar 1;36(3):456-7 MH - Adult MH - Bone Density Conservation Agents/*adverse effects/*pharmacokinetics MH - Chemistry, Pharmaceutical MH - Cholecalciferol/administration & dosage/*adverse effects/*pharmacokinetics/pharmacology MH - Cross-Over Studies MH - Diphosphonates/administration & dosage/*adverse effects/*pharmacokinetics/*pharmacology MH - Drug Combinations MH - Humans MH - Ibandronic Acid MH - Male MH - Middle Aged MH - Republic of Korea MH - Tablets MH - Therapeutic Equivalency MH - Young Adult OTO - NOTNLM OT - ibandronate OT - osteoporosis OT - pharmacokinetics OT - vitamin D(3) EDAT- 2014/01/01 06:00 MHDA- 2014/11/05 06:00 CRDT- 2014/01/01 06:00 PHST- 2013/09/09 00:00 [received] PHST- 2013/11/01 00:00 [revised] PHST- 2013/12/03 00:00 [accepted] PHST- 2014/01/01 06:00 [entrez] PHST- 2014/01/01 06:00 [pubmed] PHST- 2014/11/05 06:00 [medline] AID - S0149-2918(13)01109-0 [pii] AID - 10.1016/j.clinthera.2013.12.001 [doi] PST - ppublish SO - Clin Ther. 2014 Jan 1;36(1):48-57. doi: 10.1016/j.clinthera.2013.12.001. Epub 2013 Dec 28.