Pharmacokinetic behavior of digoxin or beta-acetyldigoxin was examined in 66 patients (27 patiets under intensive care conditions, partially with controlled breathing, 22 patients undergoing extirpation of the uterus and 17 patients treated with radium or chemotherapeutics; 19 males and 47 females) by determining plasma concentrations of digoxin (PDC). After intravenous and oral application with a maintenance dose of 0.20--0.50 mg/day blood was taken daily during a 2 to 3 week period, resulting in 510 determinations. 24 hours after the first application of 0.50 mg digoxin i.v. the mean values of PDC amounted to 0.62 +/- 0.08 ng/ml. After 0.40 or 0.25 mg digoxin per day i.v. therapeutical concentrations could be observed at the third vs fifth day. An equilibrium of PDC was reached on the 6th day after starting digitalization using maintenance doses. Intravenous application of 0.25, 0.40 or 0.50 mg digoxin per day resulted in a mean steady state of 0.68 +/- 0.37, 0.86 +/- 0.33 or 1.27 +/- 0.49 ng/ml PDC, respectively. The results were significantly different (p less than 0.01--0.001). Serial measurements indicated a great variation of PDC. In patients without renal failure the intraindividual variation of the plasma concentrations was maximal 37.4% referring to the mean steady state, interindividual 37.1% and the evaluation of the inter- and intraindividual differences amounted to 54.1%. After oral administration of digoxin (maintenance dose: 0.50 mg/day) or beta-acetyldigoxin (maintenance doses: 0.20--0.40 mg/day) differences in PDC of 38.3% and 29.7% were obtained. Body weight, age and serum creatinine concentration were partly responsible for the variance of PDC. Multiple linear regression between stead state PDC and dose, age, body weight and serum creatinine concentration revealed 62.1% of the variance of the PDC after intravenous administration of digoxin. After oral administration of beta-acetyldigoxin 39.9% were obtained. Thus, 40% of the variance were caused by differences in distribution and elimination of digoxin after i.v. application. After oral application additional 20% of the variance could be attributed to resorption and possible disturbances.
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J Chem Ecol
January 2025
Department of Nematology, University of California Riverside, Riverside, CA, USA.
Plants produce defensive toxins to deter herbivores. In response, some specialized herbivores evolved resistance and even the capacity to sequester toxins, affecting interactions at higher trophic levels. Here, we test the hypothesis that potential natural enemies of specialized herbivores are differentially affected by plant toxins depending on their level of adaptation to the plant-herbivore system.
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January 2025
Preclinical Sciences & Translational Safety, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium. Electronic address:
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January 2025
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India. Electronic address:
The biotransformation of drugs by enzymes from the human microbiome can produce active or inactive products, impacting the bioactivity and function of these drugs inside the human host. However, understanding the biotransformation reactions of drug molecules catalyzed by bacterial enzymes in human microbiota is still limited. Hence, to characterize drug utilization capabilities across all the microbial phyla inside the human gut, we have used a knowledge-based approach to develop HgutMgene-Miner software which predicts xenobiotic metabolizing enzymes (XMEs) through genome mining.
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December 2024
Department of Rehabilitation and Regenerative Medicine, College of Physicians and Surgeons, Columbia University, HHSC-1518, 701 W. 168th Street, New York, NY 10032, USA.
This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays.
View Article and Find Full Text PDFNat Med
January 2025
Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland.
The presence of circulating tumor cell (CTC) clusters is associated with disease progression and reduced survival in a variety of cancer types. In breast cancer, preclinical studies showed that inhibitors of the Na/K ATPase suppress CTC clusters and block metastasis. Here we conducted a prospective, open-label, proof-of-concept study in women with metastatic breast cancer, where the primary objective was to determine whether treatment with the Na/K ATPase inhibitor digoxin could reduce mean CTC cluster size.
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