PMID- 37077410 OWN - NLM STAT- MEDLINE DCOM- 20230421 LR - 20230421 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 17 DP - 2023 TI - Pharmacokinetic Interactions Between Bazedoxifene and Cholecalciferol: An Open-Label, Randomized, Crossover Study in Healthy Male Volunteers. PG - 1107-1114 LID - 10.2147/DDDT.S399264 [doi] AB - PURPOSE: The combined administration of bazedoxifene, a tissue-selective estrogen receptor modulator, and cholecalciferol can be a promising therapeutic option for postmenopausal osteoporosis patients. This study aimed to examine the pharmacokinetic interactions between these two drugs and the tolerability of their combined administration in healthy male subjects. PATIENTS AND METHODS: Thirty male volunteers were randomly assigned to one of the six sequences comprised of three treatments: bazedoxifene 20 mg monotherapy, cholecalciferol 1600 IU monotherapy, and combined bazedoxifene and cholecalciferol therapy. For each treatment, a single dose of the investigational drug(s) was administered orally, and serial blood samples were collected to measure the plasma concentrations of bazedoxifene and cholecalciferol. Pharmacokinetic parameters were calculated using the non-compartmental method. The point estimate and 90% confidence interval (CI) of the geometric mean ratio (GMR) were obtained to compare the exposures of combined therapy and monotherapy. The pharmacokinetic parameters compared were the maximum plasma concentration (C(max)) and the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC(last)). The safety and tolerability of the combined therapy were assessed in terms of the frequency and severity of adverse events (AEs). RESULTS: For bazedoxifene, the GMR (90% CI) of the combined therapy to monotherapy was 1.044 (0.9263-1.1765) for C(max) and 1.1329 (1.0232-1.2544) for AUC(last). For baseline-adjusted cholecalciferol, the GMR (90% CI) of the combined therapy to monotherapy was 0.8543 (0.8005-0.9117) for C(max) and 0.8056 (0.7445-0.8717) for AUC(last). The frequency of AEs observed was not significantly different between the combined therapy and monotherapy, and their severity was mild in all cases. CONCLUSION: A mild degree of pharmacokinetic interaction was observed when bazedoxifene and cholecalciferol were administered concomitantly to healthy male volunteers. This combined therapy was well tolerated at the dose levels used in the present study. CI - (c) 2023 Lee et al. FAU - Lee, Moon Hee AU - Lee MH AUID- ORCID: 0000-0001-5259-5630 AD - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea. FAU - Yoon, Seok-Kyu AU - Yoon SK AUID- ORCID: 0000-0003-1014-887X AD - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea. FAU - Kim, Hyungsub AU - Kim H AUID- ORCID: 0000-0002-8736-1655 AD - Department of Emergency Medical Services, College of Health Sciences, Eulji University, Seongnam, Republic of Korea. FAU - Cho, Yong-Soon AU - Cho YS AUID- ORCID: 0000-0003-1424-1123 AD - Department of Pharmacology and Clinical Pharmacology, Inje University College of Medicine, Busan, Republic of Korea. FAU - Han, Sungpil AU - Han S AUID- ORCID: 0000-0002-4674-7682 AD - Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Lee, Shi Hyang AU - Lee SH AUID- ORCID: 0000-0002-5565-8278 AD - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea. FAU - Bae, Kyun-Seop AU - Bae KS AUID- ORCID: 0000-0001-7399-5879 AD - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea. FAU - Jung, Jina AU - Jung J AUID- ORCID: 0000-0002-9982-6560 AD - Hanmi Pharmaceutical Co. Ltd., Seoul, Republic of Korea. FAU - Hong, Sung Hee AU - Hong SH AUID- ORCID: 0000-0003-1228-8382 AD - Hanmi Pharmaceutical Co. Ltd., Seoul, Republic of Korea. FAU - Lim, Hyeong-Seok AU - Lim HS AUID- ORCID: 0000-0003-1420-8200 AD - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea. LA - eng PT - Journal Article DEP - 20230412 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - Q16TT9C5BK (bazedoxifene) RN - 1C6V77QF41 (Cholecalciferol) SB - IM MH - Humans MH - Male MH - Cross-Over Studies MH - *Cholecalciferol/adverse effects MH - Therapeutic Equivalency MH - *Volunteers MH - Healthy Volunteers MH - Area Under Curve MH - Administration, Oral PMC - PMC10106309 OTO - NOTNLM OT - bazedoxifene OT - cholecalciferol OT - drug-drug interaction OT - pharmacokinetics OT - tolerability COIS- Hyeong-Seok Lim has received grants from Hanmi Pharmaceutical Co. Ltd. for a range of research projects, including the study reported in this article. Jina Jung and Sung Hee Hong are employees of Hanmi Pharmaceutical Co. Ltd. The remaining authors declare no competing interests in relation to this article. EDAT- 2023/04/20 06:41 MHDA- 2023/04/21 06:41 PMCR- 2023/04/12 CRDT- 2023/04/20 02:18 PHST- 2022/12/07 00:00 [received] PHST- 2023/03/14 00:00 [accepted] PHST- 2023/04/21 06:41 [medline] PHST- 2023/04/20 06:41 [pubmed] PHST- 2023/04/20 02:18 [entrez] PHST- 2023/04/12 00:00 [pmc-release] AID - 399264 [pii] AID - 10.2147/DDDT.S399264 [doi] PST - epublish SO - Drug Des Devel Ther. 2023 Apr 12;17:1107-1114. doi: 10.2147/DDDT.S399264. eCollection 2023.