Population‐Based Investigation of Relative Clearance of Digoxin in Japanese Patients by Multiple Trough Screen Analysis: An Update

Yukawa, Eiji; Honda, Tomohiro; Ohdo, Shigehiro; Higuchi, Shun; Aoyama, Toshinobu

doi:10.1002/j.1552-4604.1997.tb04766.x

Cited by 38 publications

(40 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…after Cr, WT and SPI were considered as covariates of Cl/f, the population estimate of Cl/f was 5.9 L/h with a CV of 49%, which fell within 4.4-7.7 L/h [9] and 5.2-6.3 L/h [10] in american patients (reported by Cheng et al and Bauer et al, respectively). however, Cl/f (5.9 L/h) was slightly higher than that in Korean patients (4.38 L/h) [11] (Nagaraja et al) and american patients (4.87 L/h) [12] (Sheiner et al) and lower than that in Japanese patients (10.3 L/h) [13] (Yukawa et al) and american patients (8.25 L/h) [14] (Williams et al). These differences may be related to case characteristics, different populations, population size, the length of disease course, the extent of myocardial damage and peripheral vascular tension, and/or the method of population analysis.…”

Section: Discussionmentioning

confidence: 78%

Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice

et al. 2010

View full text Add to dashboard Cite

Aim: To establish a population pharmacokinetic (PPK) model of digoxin in older Chinese patients to provide a reference for individual medication in clinical practice. Methods: Serum concentrations of digoxin and clinically related data including gender, age, weight (WT), serum creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), albumin (ALB), and co-administration were retrospectively collected from 119 older patients taking digoxin orally for more than 7 d. NONMEM software was used to get PPK parameter values, to set up a final model, and to assess the models in clinical practice. Results: Spironolactone (SPI), WT, and Cr markedly affected the clearance rate of digoxin. The final model formula is Cl/F=5.The population estimates for Cl/ F and V d /F were 5.9 L/h and 550 L, respectively. The interindividual variabilities (CV) were 49.0% for Cl/F and 94.3% for V d /F. The residual variability (SD) between observed and predicted concentrations was 0.365 μg/L. The difference between the objective function value and the primitive function value was less than 3.84 (P>0.05) by intra-validation. Clinical applications indicated that the percent of difference between the predicted concentrations estimated by the PPK final model and the observed concentrations were -4.3%−+25%. Correlation analysis displayed that there was a linear correlation between observated and predicted values (y=1.35x+0.39, r=0.9639, P<0.0001). Conclusion: The PPK final model of digoxin in older Chinese patients can be established using the NONMEM software, which can be applied in clinical practice.Keywords: digoxin; population pharmacokinetics; aging; retrospective studies; NONMEM Acta Pharmacologica Sinica advance (2010) 31: 753-758; doi: 10.1038/aps.2010.51 Original Article model, the fixed-effect model and the statistical model. The principle of the extended non-linear least squares was applied to estimate the population pharmacokinetic parameters using the patients' sparse plasma concentration data, pathological factors, physiological factors and coadministration. This paper aimed: 1) to build a population pharmacokinetic basic model of digoxin in 119 older Chinese patients; 2) to analyze the effects of fixed-effect factors such as weight, age, gender, hepatic and renal function, and concomitant medications on this model; 3) to establish the full regression model and the final model; and 4) to determine whether the final model is stable and reliable by intra-validation and clinical applications. Materials and methods Data sourcesRoutine clinical data were retrospectively collected from 119 older patients in the general hospital of the air force, PLa.

show abstract

Section: Discussionmentioning

confidence: 78%

Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The multiple trough screen analysis has been successfully used to compute pharmacokinetic parameters in patient populations receiving drugs for treatment of disease states and it allows the identification of important patient factors that influence drug disposition [18][19][20][21]. This approach could be used as a way to identify and quantitate the effect of drug interactions in patients receiving drug combinations for therapeutic purposes.…”

Section: Discussionmentioning

confidence: 99%

“…The MAE and standard deviation for the predicted concentrations were 0.15 AE 0.12 ng/ml. The proposed method was superior in precision to the other methods [10,[15][16][17][18](see Appendix A, Table 5). …”

Section: Validationmentioning

confidence: 95%

Pharmacoepidemiologic detection of calcium channel blocker‐induced change on digoxin clearance using multiple trough screen analysis

Suematsu

Yukawa

et al. 2002

Biopharm & Drug Disp

Self Cite

View full text Add to dashboard Cite

Nonlinear mixed effects modeling was used to estimate the effects of digoxin-calcium channel blockers (verapamil, diltiazem, nifedipine) in 336 serum levels gathered from 172 patients (104 male and 68 female) receiving oral digoxin as hospital in-patients. The final model describing digoxin clearance (CL) was CL (l/day)=(87.9+2.71C(cr))0.872(CCB)0.880(CHF)0.937(SPI)0.854(DFAC), where C(cr) is the estimated creatinine clearance (ml/min); CCB=1 for concomitant administration of calcium channel blockers and CCB=zero otherwise; CHF=1 for the patients with congestive heart failure and CHF=zero otherwise; SPI=1 for concomitant administration of spironolactone and SPI=zero otherwise; DFAC=1 for administration of a half-tablet of digoxin and DFAC=zero otherwise. Concomitant administration of calcium channel blockers resulted in a 13% decrease in digoxin relative clearance.

show abstract

“…In addition, renal clearance or glomerular filtration rate in women is 10 to 25 % slower than in men even after adjusting for body size [6][7][8]. Thus, cardiovascular medications that undergo primary renal elimination, such as digoxin, will be cleared more slowly [6,7,14].…”

Section: Pharmacokineticsmentioning

confidence: 99%

Gender Differences in Cardiovascular Drugs

Stolarz

Rusch

2015

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

The different responses of women and men to cardiovascular drugs reflect gender -specific variances in pharmacokinetic profiles and drug sensitivities coupled to inherent differences in the underlying physiology of each sex. Thus, many common cardiovascular drugs exhibit gender -specific therapeutic and adverse effects. For example, the QT interval of the electrocardiogram is longer in women compared to men, and accordingly, drugs that prolong the QT interval are more likely to cause lethal ventricular arrhythmias in female than male patients. As more clinical drug trials include women subjects, our improved knowledge base for assessing the risk/benefit ratio for cardiovascular drugs in women will enable us to consider gender as one factor in prescribing drugs and adjusting drug loading and maintenance dosages. This short review will present evidence for gender- related differences in the responses to common cardiovascular drugs including statins, antiplatelet and antithrombotic agents, β-blockers, digoxin, vasodilator therapies, and drugs associated with the Long QT Syndrome.

show abstract

Population‐Based Investigation of Relative Clearance of Digoxin in Japanese Patients by Multiple Trough Screen Analysis: An Update

Cited by 38 publications

References 21 publications

Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice

Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice

Pharmacoepidemiologic detection of calcium channel blocker‐induced change on digoxin clearance using multiple trough screen analysis

Gender Differences in Cardiovascular Drugs

Contact Info

Product

Resources

About