Pharmacokinetic comparison between fixed-dose combination of fimasartan/amlodipine 60/10 mg and the corresponding loose combination through partial replicated crossover study in healthy subjects

Combination therapies of antihypertensive drugs are recommended in cases where hypertension is not controlled by monotherapy. This study aimed to compare the pharmacokinetics (PKs) between fixed-dose combination (FDC) of fimasartan/amlodipine 60/10 mg and the corresponding loose combination. Because of the high intra-subject variability for maximum plasma concentration (C(max)) of fimasartan, a randomized, open-label, 3×3 partial replicated crossover design was adopted. Subjects received a single dose of FDC of fimasartan/amlodipine 60/10 mg or the corresponding loose combination in each period. Blood samples for PK analysis were collected up to 48 hours for fimasartan and 144 hours for amlodipine, respectively. Geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) of the FDC to the loose combination for C(max) and area under the concentration-time curve from time 0 to the last quantifiable time point (AUC(last)) were calculated. Sixty healthy subjects were randomized, and 57 subjects completed the study. The concentration-time profiles of fimasartan and amlodipine were similar between the FDC and loose combination. The GMRs (90% CIs) of the FDC to the loose combination for C(max) and AUC(last) were 1.0440 (0.9202–1.1844) and 1.0412 (0.9775–1.1090) for fimasartan, and 1.0430 (1.0156–1.0711) and 1.0339 (1.0055–1.0631) for amlodipine, respectively. The GMRs and its 90% CIs for C(max) and AUC(last) of fimasartan and amlodipine were included not only in the scaled bioequivalence criteria but also in the conventional bioequivalence criteria. In conclusion, FDC of fimasartan/amlodipine 60/10 mg showed comparable PK profiles with the corresponding loose combination, which suggests their bioequivalence.

Use of Molecular Imaging in Clinical Drug Development: a Systematic Review / 대한핵의학회잡지

BACKGROUND: Molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can provide the crucial pharmacokinetic-pharmacodynamic information of a drug non-invasively at an early stage of clinical drug development. Nevertheless, not much has been known how molecular imaging has been actually used in drug development studies.METHODS: We searched PubMed using such keywords as molecular imaging, PET, SPECT, drug development, and new drug, or any combination of those to select papers in English, published from January 1, 1990, to December 31, 2015. The information about the publication year, therapeutic area of a drug candidate, drug development phase, and imaging modality and utility of imaging were extracted.RESULTS: Of 10,264 papers initially screened, 208 papers met the eligibility criteria. The more recent the publication year, the bigger the number of papers, particularly since 2010. The two major therapeutic areas using molecular imaging to develop drugs were oncology (47.6%) and the central nervous system (CNS, 36.5%), in which efficacy (63.5%) and proof-of-concept through either receptor occupancy (RO) or other than RO (29.7%), respectively, were the primary utility of molecular imaging. PET was used 4.7 times more frequently than SPECT. Molecular imaging was most frequently used in phase I clinical trials (40.8%), whereas it was employed rarely in phase 0 or exploratory IND studies (1.4%).CONCLUSIONS: The present study confirmed the trend that molecular imaging has been more actively employed in recent clinical drug development studies although its adoption was rather slow and rare in phase 0 studies.

Use of Molecular Imaging in Clinical Drug Development: a Systematic Review / 대한핵의학회잡지

BACKGROUND@#Molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can provide the crucial pharmacokinetic-pharmacodynamic information of a drug non-invasively at an early stage of clinical drug development. Nevertheless, not much has been known how molecular imaging has been actually used in drug development studies.@*METHODS@#We searched PubMed using such keywords as molecular imaging, PET, SPECT, drug development, and new drug, or any combination of those to select papers in English, published from January 1, 1990, to December 31, 2015. The information about the publication year, therapeutic area of a drug candidate, drug development phase, and imaging modality and utility of imaging were extracted.@*RESULTS@#Of 10,264 papers initially screened, 208 papers met the eligibility criteria. The more recent the publication year, the bigger the number of papers, particularly since 2010. The two major therapeutic areas using molecular imaging to develop drugs were oncology (47.6%) and the central nervous system (CNS, 36.5%), in which efficacy (63.5%) and proof-of-concept through either receptor occupancy (RO) or other than RO (29.7%), respectively, were the primary utility of molecular imaging. PET was used 4.7 times more frequently than SPECT. Molecular imaging was most frequently used in phase I clinical trials (40.8%), whereas it was employed rarely in phase 0 or exploratory IND studies (1.4%).@*CONCLUSIONS@#The present study confirmed the trend that molecular imaging has been more actively employed in recent clinical drug development studies although its adoption was rather slow and rare in phase 0 studies.