A prospective cross-over study was performed in a general practice environment to assess and compare compliance data obtained by electronic monitoring on a BID or QD regimen in 113 patients with hypertension or angina pectoris. All patients were on a BID regimen (nifedipine SR) during the first month and switched to QD regimen (amlodipine) for another month. Taking compliance (i.e. the proportion of days with correct dosing) improved in 30% of patients (95% confidence interval 19 to 41%, p < 0.001), when switching from a BID to a QD regimen, but at the same time there was a 15% increase (95% confidence interval 5 to 25%, p < 0.02) in the number of patients with one or more no-dosing days. About 8% of patients had a low compliance rate, irrespective of the dosage regimen. Actual dosage intervals were used to estimate extent and timing of periods with unsatisfactory drug activity for various hypothetical drug durations of action, and it appears that the apparent advantage of QD regimen in terms of compliance is clinically meaningful only, when the duration of activity extents beyond the dosage interval in all patients.
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Cancer Chemother Pharmacol
January 2025
Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Background: ATR is an apical DDR kinase activated at damaged replication forks. Elimusertib is an oral ATR inhibitor and potentiates irinotecan in human colorectal cancer models.
Methods: To establish dose and tolerability of elimusertib with FOLFIRI, a Bayesian Optimal Interval trial design was pursued.
Infect Drug Resist
January 2025
Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China.
Background: Contezolid (CZD) is an analog of Linezolid (LZD) that has demonstrated potent in vitro and in vivo activity against tuberculosis (TB) while presenting a safer side-effect profile. In this study, we evaluated the early bactericidal activity (EBA) of CZD compared to LZD, with LZD serving as a control.
Methods: Naive, smear-positive pulmonary TB patients were enrolled and randomly assigned to receive either a 14-day monotherapy regimen of 600 mg LZD once daily (QD) or 800 mg CZD twice daily (BID).
Clin Cancer Res
January 2025
The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Purpose: More active high-dose chemotherapy (HDC) regimens are needed for autologous stem-cell transplantation (ASCT) for refractory lymphomas. Seeking HDC enhancement with a poly(ADP-ribose) polymerase (PARP) inhibitor, we observed marked synergy between olaparib and vorinostat/gemcitabine/busulfan/melphalan (GemBuMel) against lymphoma cell lines, mediated by inhibition of DNA damage repair. Our preclinical work led us to clinically study olaparib/vorinostat/GemBuMel with ASCT.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Medical Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, China.
Patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) who fail first- and second-line treatments face significant challenges in third-line therapy, where monotherapies often yield poor outcomes and limited survival benefits. The prognosis is particularly poor for mCRC with the unique molecular subtype of BRAF V600E mutation. This report describes sustained benefits from a third-line treatment regimen (SFS) combining tegafur/gimeracil/oteracil (S-1), fruquintinib, and sintilimab in a patient with BRAF V600E-mutated MSS mCRC.
View Article and Find Full Text PDFEpilepsia
December 2024
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Objective: We aimed to quantify and predict lacosamide exposure during pregnancy by developing a pregnancy physiologically-based pharmacokinetic model, allowing the prediction of potential dose increases to support maintaining a patient's preconception lacosamide concentrations.
Methods: Models for nonpregnant adults and pregnant female patients were constructed using physiochemical and pharmacological parameters identified from literature review. Evaluation of plasma concentration data from human males was digitized from the literature.
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