Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new lanoxin research articles will be listed here shortly after becoming available to us.
Related Sponsors
Medical research on lanoxin
Absence of an effect of a single-dose deferasirox on the steady-state pharmacokinetics of digoxin.
Int J Clin Pharmacol Ther. 2008 Oct; Volume 46(October): 519-526
Sechaud1 R, Robeva2 A, Belleli1 R, Balez3 S
Deferasirox (Exjade(R), ICL670) is a potent iron chelator, recently approved as first-line therapy for the treatment of blood-transfusion-related iron overload. Iron deposition in the heart may lead to cardiac dysfunction in patients with iron overload. Thus, the combination of cardiac glycosides and deferasirox is likely to be used in clinical practice. Objective: This study was designed to investigate the effect of deferasirox on steady-state pharmacokinetics of digoxin. As digoxin is a P-glycoprotein substrate, the trial also explored the potential of deferasirox to alter the pharmacokinetics of compounds transported by P-glycoprotein in general. Methods: An open-label, randomized, 2-period, crossover study was carried out with 16 healthy volunteers. During both treatment periods, each subject received daily oral doses of digoxin for 8 days (0.5 mg on Day 1 and 0.25 mg/day on Days 2 - 8). In one of these treatment periods, single oral deferasirox 20 mg/kg was coadministered with digoxin on Day 8. Pharmacokinetic parameters assessed at the end of each treatment period were compared using the standard statistical analysis for bioequivalence assessment. Results: Deferasirox did not alter the steady-state pharmacokinetics of digoxin. The geometric mean ratios and 90% confidence intervals for Cmax and AUCtau of digoxin (with/without deferasirox) were 0.93 (0.82 - 1.06) and 0.91 (0.83 - 1.00), respectively, and thus within the equivalence limits of 0.8 - 1.25. The amount of digoxin excreted intact in urine was similarly unaltered by coadministration of deferasirox. Conclusions: This study shows that single-dose deferasirox has no effect on steady-state pharmacokinetics of digoxin. Therefore, no dose adjustment of digoxin is necessary when deferasirox and digoxin are coadministered. The lack of interaction suggests that deferasirox is unlikely to interact with P-glycoprotein substrates.
Ther Drug Monit. 2008 Sep 26;
Dasgupta A, Tso G, Wells A
Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with digoxin in clinical practice. It has been well documented in the literature that spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with several digoxin immunoassays at concentrations expected after therapeutic usage of these drugs and falsely elevate or lower serum digoxin concentrations. Recently, Abbott Laboratories marketed a new Digoxin III immunoassay for application on the AxSYM analyzer. We studied the potential interference of these compounds with this new digoxin assay. The Tina-quant assay was used as the reference method because spironolactone, potassium canrenoate, and canrenone do not interfere with serum digoxin measurement using this assay. Aliquots of drug-free serum were supplemented with therapeutic and above therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent digoxin concentrations were measured using the Digoxin III assay and Tina-quant assay. Significant apparent digoxin concentrations were observed when the Digoxin III digoxin assay was used, but no apparent digoxin levels was observed using the Tina-quant assay. When serum pools prepared from patients receiving digoxin were further supplemented with these compounds in concentrations expected in sera of patients receiving these medications, falsely elevated digoxin levels were observed using Digoxin III assay, but no statistically significant change was observed using the Tina-quant assay. We conclude that spironolactone, potassium canrenoate, and their common metabolite canrenone interfere with the serum digoxin measurements using the new Digoxin III assay.
Digoxin-specific Fab fragments as single first-line therapy in digitalis poisoning.
Crit Care Med. 2008 Sep 26;
Lapostolle F, Borron SW, Verdier C, Taboulet P, Guerrier G, Adnet F, Clemessy JL, Bismuth C, Baud FJ
OBJECTIVE:: Despite administration of Fab fragments in digitalis poisoning, high mortality rates are consistently reported. A previous study suggested that Fab fragments prescribed as first-line therapy might improve mortality rate. Our objective was to evaluate this approach. DESIGN:: Retrospective chart review (January 1990 to January 2004). SETTING:: University hospital intensive care unit. PATIENTS:: Consecutive patients admitted for cardiac glycoside poisoning. INTERVENTION:: First-line therapy with Fab fragments (with or without atropine) in either curative or prophylactic doses. MEASUREMENTS AND MAIN RESULTS:: A total of 141 patients were admitted for digitalis poisoning of whom 66 received first-line Fab fragment therapy. Their median age was 74 yrs (25-75 percentiles: 51-83); 76% were women. Half were intoxicated by digitoxin and half by digoxin. Median serum concentration was 168 (108-205) ng/mL for digitoxin and 6.2 (4.3-13.5) ng/mL for digoxin. Conduction disturbances were reported in 45 cases (68%) and ventricular arrhythmia in six cases (9%). Fab fragments were administered as curative treatment in 21 patients (32%) and prophylactically in 45 patients (68%). The median cumulative dose was 4 (4-6) vials. No adverse effects were reported. Five patients died (7.6%). CONCLUSIONS:: First-line therapy with Fab fragments in patients with digitalis poisoning was associated with a low mortality rate.
Evaluation of the pharmacokinetics of digoxin in healthy subjects receiving etoricoxib.
Br J Clin Pharmacol. 2008 Sep 24;
Schwartz JI, Agrawal NG, Wehling M, Musser BJ, Gumbs CP, Michiels N, De Smet M, Wagner JA
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Digoxin is a well-recognized inotropic agent with a narrow therapeutic index. * Nonsteroidal anti-inflammatory drugs, including the selective cyclooxygenase-2 inhibitor etoricoxib, are very likely to be used in patients receiving digoxin due to the similar populations requiring the drugs. * Digoxin drug interactions should be assessed and described to clinicians when new drugs become available. WHAT THIS STUDY ADDS * This study is the first to provide the practitioner with a detailed description of the influence of etoricoxib on the pharmacokinetics of digoxin. * Due to the methods used, it shows that etoricoxib does not interfere with P-glycoprotein in the kidney, a method of digoxin disposition. * In addition, this paper provides confidence to the practitioner that there will be no clinically important reason to avoid the combination of the two drugs. AIMS Digoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index. The aim was to investigate whether the cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug etoricoxib affects the steady-state pharmacokinetics of digoxin. METHODS This was a double-blind, randomized, placebo-controlled, two-period cross-over study. In each period, 14 healthy volunteers ranging in age from 21 to 35 years received oral digoxin 0.25 mg daily and were randomized to either etoricoxib 120 mg or matching placebo tablets once daily for 10 days. Trough digoxin plasma concentrations were analysed by linear regression to examine digoxin accumulation over time. RESULTS The geometric mean ratios (etoricoxib/placebo) for AUC(0-24h), C(max) and urinary excretion were 1.06 (90% confidence interval 0.97, 1.17), 1.33 (1.21, 1.46) and 1.10 (1.00, 1.20), respectively. The median (range) for digoxin T(max) (h) values with etoricoxib and placebo were 0.5 (0.5, 1.5) and 1.0 (0.5, 1.5), respectively. Steady-state digoxin plasma concentrations were achieved by day 7 in each treatment period. No serious adverse experiences were reported. CONCLUSIONS Although etoricoxib 120 mg did produce an approximately 33% increase in digoxin C(max), this increase does not appear to be clinically meaningful, as cardiotoxicity with digoxin has been associated with elevations in steady-state rather than peak concentrations. From these results, it appears that etoricoxib does not cause any changes in digoxin steady-state pharmacokinetics that would necessitate a dose adjustment.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2008 Jul; 28(7): 662-5
Bi YF, Mao JY, Liu CX
Since Chinese herbal drugs and their preparations were usually applied in combining with digoxin in modern clinical practice, high attention was accordingly widely paid to their impacts on the pharmacokinetics of digoxin. The researches in the recent years dealing with this topic were reviewed in the paper, involving the Chinese herbs, including Radix Ginseng, Radix Salviae Miltiorrhizae, Venenum Bufonis, Folium Seu Cortex Nerii Indici, St John's wort, Fructus Crataegi, and Semen Ginkgo, as well as the Chinese herbal preparations including Shengmai Injection, Milkvetch Injection, Liushen Pill, Kyushin, and Di'ao Xinxuekang, etc.
Lik Sprava. 2008 Jan-Feb; 60-6
Leterature data and own investigations are summarized in the article. New experimental facts about mechanism of action of cardiac glycosides (especially digoxin) were obtained last year. It was shown that in human organism there are endogenous cardiosteroids (digitalis-like substances, endogenous oubain and other). They are in different organs (adrenal glands, hypothalamus, pituitary gland) and have influence on different organs and systems. Indications, contraindications, side effects, interactions with other drugs have been studied by cardiologists. Results of international multicentere studies demonstrate high efficacy of digoxin in treatment of chronic heart failure caused by compromised contractile activity of myocardium, atrium fibrillation and is used for controlling number of heart contractions and supraventricular paroxysmal tachycardia. More than 200 years history of scientific researches and clinical use of cardiac glycosides show that this group of medicine may be applied in a combine pharmacotherapy of chronic heart failure together with antihypertensive drugs.
Phytochem Anal. 2008 Sep 25;
Balsevich JJ, Bishop GG, Deibert LK
INTRODUCTION: Saponins are widely distributed complex plant glycosides possessing a variety of structure-dependent bioactivities. Quantitation of individual saponins is difficult due to lack of available standards, mainly as a consequence of purification difficulties. Determination of total saponin content can be problematic, often relying on non-specific methods based on butanol solubility, haemolytic activity or formation of coloured derivatives. OBJECTIVE: To develop a general quantitative method based on the use of the readily available cardenolides, digitoxin (1) and digoxin (2), as internal standards in an HPLC-PAD-based analysis. METHODOLOGY: The cardenolides were run at a variety of concentrations to establish linearity and reproducibility of detector response and then evaluated as internal standards for quantitation of triterpene saponins in several plant-derived extracts by HPLC-PAD. Mixtures of saponins, largely freed from other extractables, were obtained by fractionation of total extracts on solid phase extraction columns (SPE) employing a water-methanol gradient and used for construction of calibration curves. Saponin identification and structural information was obtained via a single quadrupole mass detector using electrospray ionisation in negative ion mode (ESI(-)). RESULTS: Saponin contents in six samples from five species were determined and compared with literature results and a gravimetric method based on butanol-water partitioning. Results were generally consistent with literature reports and superior to gravimetric butanol-water partitioning. CONCLUSION: Digitoxin and digoxin are useful as internal standards in HPLC estimation of saponin content. Saponins from different species having similar structures and molecular weights afford similar calibration curves. Copyright (c) 2008 John Wiley & Sons, Ltd.
J Pharm Pharmacol. 2008 Oct; 60(10): 1305-10
Manford F, Riffo-Vasquez Y, Spina D, Page CP, Hutt AJ, Moore V, Johansson F, Forbes B
Although in-vitro experiments have suggested that P-glycoprotein (P-gp) may have an important influence on the disposition of inhaled drugs, the effect of P-gp on absorption from the lung in-vivo has not been reported previously. The aim of this study was to compare the pulmonary absorption of digoxin, a well-characterised substrate for P-gp, in mdr1a (-/-) (P-gp-deficient) and mdr1a (+/+) (P-gp-competent) mice. Digoxin was administered by intratracheal instillation over 3-4 s, a method demonstrated to result in dispersion of the dose to all regions of the lung. Drug distribution was determined in the lungs, plasma, brain, heart, liver and kidney of individual mice after 5, 10, 30, 60 and 90 min. Digoxin was cleared rapidly from the lung after intratracheal administration. No differences were observed in the maximum serum concentrations between mdr1a (+/+) and mdr1a (-/-) mice (37.8 +/- 6.9 and 38.8 +/- 15.8 ng mL(-1), respectively). The serum concentration versus time profiles were similar in both strains; the area under the drug serum concentration versus time curve (AUC) was 2010 and 1812 ng mL(-1) min in mdr1a (-/-) and mdr1a (+/+) mice, respectively. For organs harvested at the end of the experiment (90 min), the only significant difference between the strains was the markedly elevated concentration of digoxin in the brains of mdr1a (-/-) mice. In conclusion, digoxin is rapidly absorbed from the mouse lung following tracheal instillation, with no difference in the rate or extent of absorption between mdr1a-deficient and -competent mice. This suggests that, in contrast to the scenario suggested by in-vitro data, P-gp in the respiratory epithelium may have little influence on the disposition of drugs that are well absorbed from the lung.
Pharmacology. 2008 Sep 23; 82(3): 221-227
Xu P, Jiang ZP, Zhang BK, Tu JY, Li HD
Objective: To investigate the effect of single-nucleotide polymorphisms (SNPs) and the haplotypes of MDR1 on the pharmacokinetics of single-dose digoxin in healthy Chinese volunteers. Methods: After the genotypes of the MDR1 alleles of interest (G1199A, C1236T, G2677T/A and C3435T) had been determined, 20 subjects with the predominant haplotypes (TTT, CGC, TGC and CAC, in the order of position 1236-2677-3435) were selected and administered with 0.25 mg of digoxin. Venous blood samples were taken from 0 to 4 h after dosing, and the pharmacokinetic parameters were calculated using the Drug and Statistics software. Results: No mutation allele of G1199A was found in this study, the frequencies of the C1236T, G2677T/A and C3435T genetic variants were 65.2, 41.2, 17.3 and 39.7%, respectively. The 4 haplotypes TTT, TGC, CGC and CAC were present in more than 90% of Chinese Han subjects, and an incomplete linkage between C3435T in exon 26, G2677T in exon 21 and C1236T in exon 12 was found. The peak concentration in plasma, the time to reach the peak concentration and the area under the plasma concentration/time curve between 0 and 4 h were used as indices of digoxin absorption. They were significantly different between subjects with the haplotypes TGC-CGC and those with TTT-TTT (p < 0.05). No significant difference was found when volunteers were grouped according to the haplotypes derived from G2677T and C3435T or disparate SNPs. Conclusion: Our findings indicated that the MDR1 haplotype derived from C1236T, G2677T/A and C3435T is superior to predict the pharmacokinetics of digoxin. Digoxin pharmacokinetics are significantly different between individuals with the TTT-TTT haplotype and those with TGC-CGC.
Devious digoxin: a case review.
J Emerg Nurs. 2008 Oct; 34(5): 487-9
Kemmerer DA