1.
Comparison of Pharmacokinetics of a Fixed-Dose Combination of Amlodipine/Losartan/Rosuvastatin with Concomitant Administration of Amlodipine/Losartan and Rosuvastatin in Healthy Volunteers.
Yoon, DY, Park, SI, Jung, JA, Kim, YI, Jang, IJ, Chung, JY
Drug design, development and therapy. 2020;:661-668
Abstract
BACKGROUND A fixed-dose combination (FDC) tablet formulation of amlodipine/losartan/rosuvastatin 5/100/20 mg was developed to improve medication compliance in patients with both hypertension and dyslipidemia. The comparative pharmacokinetic study was performed to compare the profile of an FDC tablet formulation of amlodipine/losartan/rosuvastatin with that of concomitant administration of a currently marketed FDC tablet of amlodipine/losartan with a rosuvastatin tablet. SUBJECTS AND METHODS A randomized, open-label, single oral dose, two-way crossover study was conducted in 60 healthy subjects. Subjects were orally administered the FDC tablet of amlodipine/losartan/rosuvastatin and a loose combination (LC) of two tablets comprising an FDC of amlodipine/losartan and rosuvastatin. Blood samples were collected for up to 144 h post dose for pharmacokinetic evaluations. Plasma concentrations of amlodipine, losartan, EXP3174 (an active metabolite of losartan), and rosuvastatin were measured by using liquid chromatography-tandem mass spectrometry. The geometric mean ratio (GMR) and its 90% confidence interval (90% CI) in the FDC treatment to LC treatment for the area under the concentration-time curve from zero to the last quantifiable time point (AUClast) and the maximum plasma concentration (Cmax) were calculated. Safety was monitored throughout the study. RESULTS The GMR (90% CI) values of AUClast and Cmax were 0.9946 (0.9663-1.0238) and 0.9690 (0.9379-1.0011) for amlodipine, 0.9855 (0.9422-1.0308) and 0.9178 (0.8349-1.0089) for losartan, 0.9814 (0.9501-1.0136) and 0.9756 (0.9313-1.0219) for EXP3174, and 0.9448 (0.8995-0.9923) and 0.9609 (0.8799-1.0494) for rosuvastatin, respectively. No clinically significant changes were observed in any of the safety parameters, including clinical laboratory tests, vital signs, electrocardiograms, and physical examinations, between the FDC treatment and the LC treatment. CONCLUSION We confirmed the pharmacokinetic equivalence of the FDC and LC treatments. This triple combination FDC formulation could be a clinically useful replacement for LC therapy.
2.
Prognostic factors in second-line treatment of urothelial cancers with gemcitabine and paclitaxel (German Association of Urological Oncology trial AB20/99).
Niegisch, G, Fimmers, R, Siener, R, Park, SI, Albers, P, ,
European urology. 2011;(5):1087-96
Abstract
BACKGROUND In the treatment of urothelial cancer, identification of patients who are likely to benefit from further therapy after cisplatin failure is crucial for reasonable treatment decisions. OBJECTIVE Validate the prognostic factor model (PFM) for survival developed by Bellmunt et al. in a different patient cohort with a different chemotherapy regimen. DESIGN, SETTING, AND PARTICIPANTS Baseline parameters of 102 patients treated within a randomized phase 3 trial of second-line gemcitabine and paclitaxel (GP) comparing short-term to prolonged chemotherapy (German Association of Urological Oncology trial AB20/99) were analyzed. Patients were stratified according to the PFM based on a score including performance status, presence of hepatic metastases, and hemoglobin levels. MEASUREMENTS The baseline parameters of the GP cohort were compared with those of patients treated in the phase 3 trial of vinflunine versus best supportive care. Univariate and multivariate analyses of baseline parameters with respect to overall survival (OS) and treatment response were performed. OS of patients stratified according to the PFM was compared by log-rank test. RESULTS AND LIMITATIONS The vinflunine and the GP cohorts differed, as patients after perioperative (neoadjuvant or adjuvant) treatment were included in the latter cohort. According to the PFM, prognostic subgroups with significant difference in OS (11.8 mo [95% confidence interval (CI), 6.3-17.3], 8.1 mo [95% CI, 4.8-11.4], 3.2 mo [95% CI, 0.0-7.9]; p=0.007) were identified. The PFM identified risk groups in patients with failed treatment of metastatic disease (14.1 mo [95% CI, 8.9-19.3], 7.3 mo [95% CI, 0.0-17.8], 3.8 mo [95% CI, 0.0-9.0]; p=0.006) but not in patients treated (neo)adjuvantly. Lymph node-only disease was a strong predictor of treatment response that overruled every other single predictive parameter (0.284, p=0.0266). CONCLUSIONS The PFM was successfully validated in the GP and should be used to tailor second-line treatment strategy. Patients with lymph node-only disease may benefit from second-line treatment even if anemia or impaired performance status is present. TRIAL REGISTRATION German Cancer Society 01-09 (www.krebsgesellschaft.de).
3.
Randomized crossover study to assess the inter- and intrasubject variability of morning mycophenolic acid concentrations from enteric-coated mycophenolate sodium and mycophenolate mofetil in stable renal transplant recipients.
Tedesco-Silva, H, Felipe, CR, Park, SI, Pinheiro-Machado, PG, Garcia, R, Slade, A, Schmouder, R, Medina-Pestana, JO
Clinical transplantation. 2010;(4):E116-23
Abstract
The delayed release of mycophenolic acid (MPA) from enteric-coated mycophenolate sodium (EC-MPS, myfortic®) may have an impact on the variability of MPA trough (C0 h) levels. A randomized, two-period crossover study was performed in 24 maintenance renal transplants to evaluate the inter- and intrasubject variability of MPA predose levels from EC-MPS and mycophenolate mofetil (MMF, CellCept®), both in combination with cyclosporine. Patients received EC-MPS (720 mg b.i.d.) and MMF (1000 mg b.i.d.) for a period of 21 d each. MPA plasma levels were measured over the final seven consecutive days at -1, 0, 1, 2, and 3 h after the morning MPA dose. Intersubject coefficients of variation (%CV) for MPA troughs were 47.5% (95% CI, 34.1-80.3) and 54.4% (40.0-86.8) for EC-MPS and MMF, respectively; intrasubject %CVs were 62.7% (55.1-72.9) and 42.8% (37.9-49.2). High MPA C0 h levels>10 μg/mL were rarely observed with both EC-MPS (1.8%) and MMF (0.6%). Mean MPA area under the curve (AUC)0-3 h was comparable between treatments, while MPA C0 h was on average 46% higher with EC-MPS. In conclusion, predose MPA trough level monitoring appears of limited value during EC-MPS and MMF therapy given the large intrasubject variability in MPA C0 h levels with both treatments.