Mariam Abdel Jalil1, Noura Abdullah2, Mervat Alsous3, Khawla Abu-Hammour4. 1. Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, University of Jordan, Amman, 11942, Jordan. M.Abdeljalil01@ju.edu.jo. 2. Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman, Jordan. 3. Department of Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan. 4. Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, University of Jordan, Amman, 11942, Jordan.
Abstract
BACKGROUND: Digoxin is a cardiac glycoside that was introduced to cardiovascular medicine more than 200 years ago. Its use is associated with large variability, which complicates achieving the desired therapeutic outcomes. OBJECTIVES: To present a synthesis of the available literature on the population pharmacokinetics of digoxin in adults and to identify the sources of variability in its pharmacokinetics. METHODS: This is a PROSPERO registered systematic review (CRD42018105300). A literature search was conducted using the ISI Web of Science, Science Direct, PubMed, and SCOPUS databases to identify digoxin population pharmacokinetic studies of adults that utilized the nonlinear mixed-effect modeling approach. RESULTS: Sixteen articles were included in the present analysis. Only two studies were conducted in elderly subjects as a separate population. Both the pharmacokinetics and pharmacodynamics of digoxin were investigated in one study. Furthermore, the reviewed studies were mostly conducted in East Asian populations (68.8%). Digoxin's pharmacokinetics were usually described by a one-compartment model because of the nature of the collected data. Weight, age, kidney function, presence of heart failure, and co-administered medications such as calcium channel blockers were the most commonly identified predictors of digoxin clearance. The value of apparent clearance in a typical study individual ranged from 0.005 to 0.2 l/h/kg, while the value of the apparent volume of distribution ranged from 3.14 to 15.2 l/kg. The quality of model evaluation was deemed excellent only in 31.3% of the studies. CONCLUSION: This review provides information about variables that need to be considered when prescribing digoxin. The results highlight the need for prospective studies that allow two-compartment pharmacokinetic/pharmacodynamic models to be established, with a special focus on the elderly subpopulation.
BACKGROUND:Digoxin is a cardiac glycoside that was introduced to cardiovascular medicine more than 200 years ago. Its use is associated with large variability, which complicates achieving the desired therapeutic outcomes. OBJECTIVES: To present a synthesis of the available literature on the population pharmacokinetics of digoxin in adults and to identify the sources of variability in its pharmacokinetics. METHODS: This is a PROSPERO registered systematic review (CRD42018105300). A literature search was conducted using the ISI Web of Science, Science Direct, PubMed, and SCOPUS databases to identify digoxin population pharmacokinetic studies of adults that utilized the nonlinear mixed-effect modeling approach. RESULTS: Sixteen articles were included in the present analysis. Only two studies were conducted in elderly subjects as a separate population. Both the pharmacokinetics and pharmacodynamics of digoxin were investigated in one study. Furthermore, the reviewed studies were mostly conducted in East Asian populations (68.8%). Digoxin's pharmacokinetics were usually described by a one-compartment model because of the nature of the collected data. Weight, age, kidney function, presence of heart failure, and co-administered medications such as calcium channel blockers were the most commonly identified predictors of digoxin clearance. The value of apparent clearance in a typical study individual ranged from 0.005 to 0.2 l/h/kg, while the value of the apparent volume of distribution ranged from 3.14 to 15.2 l/kg. The quality of model evaluation was deemed excellent only in 31.3% of the studies. CONCLUSION: This review provides information about variables that need to be considered when prescribing digoxin. The results highlight the need for prospective studies that allow two-compartment pharmacokinetic/pharmacodynamic models to be established, with a special focus on the elderly subpopulation.
Authors: Emelia J Benjamin; Salim S Virani; Clifton W Callaway; Alanna M Chamberlain; Alexander R Chang; Susan Cheng; Stephanie E Chiuve; Mary Cushman; Francesca N Delling; Rajat Deo; Sarah D de Ferranti; Jane F Ferguson; Myriam Fornage; Cathleen Gillespie; Carmen R Isasi; Monik C Jiménez; Lori Chaffin Jordan; Suzanne E Judd; Daniel Lackland; Judith H Lichtman; Lynda Lisabeth; Simin Liu; Chris T Longenecker; Pamela L Lutsey; Jason S Mackey; David B Matchar; Kunihiro Matsushita; Michael E Mussolino; Khurram Nasir; Martin O'Flaherty; Latha P Palaniappan; Ambarish Pandey; Dilip K Pandey; Mathew J Reeves; Matthew D Ritchey; Carlos J Rodriguez; Gregory A Roth; Wayne D Rosamond; Uchechukwu K A Sampson; Gary M Satou; Svati H Shah; Nicole L Spartano; David L Tirschwell; Connie W Tsao; Jenifer H Voeks; Joshua Z Willey; John T Wilkins; Jason Hy Wu; Heather M Alger; Sally S Wong; Paul Muntner Journal: Circulation Date: 2018-01-31 Impact factor: 29.690
Authors: Suveen Angraal; Sudhakar V Nuti; Frederick A Masoudi; James V Freeman; Karthik Murugiah; Nilay D Shah; Nihar R Desai; Isuru Ranasinghe; Yun Wang; Harlan M Krumholz Journal: Am J Med Date: 2019-05-09 Impact factor: 4.965