Where does hydrolysis of nandrolone decanoate occur in the human body after release from an oil depot?

Kalicharan, R.W.; Bout, Marie-Adélaïde; Oussoren, Christien; Vromans, Herman

doi:10.1016/j.ijpharm.2016.10.068

Cited by 13 publications

(7 citation statements)

References 25 publications

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“…Many AASs can be administrated in parenteral or oral ways, causing different metabolism altering androgenic or anabolic effects. ND is injected intramuscularly with an oil that delays absorption and is not hepatotoxic [ 16 , 117 ].…”

Section: Discussionmentioning

confidence: 99%

Nandrolone Decanoate: Use, Abuse and Side Effects

et al. 2020

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Background and Objectives: Androgens play a significant role in the development of male reproductive organs. The clinical use of synthetic testosterone derivatives, such as nandrolone, is focused on maximizing the anabolic effects and minimizing the androgenic ones. Class II anabolic androgenic steroids (AAS), including nandrolone, are rapidly becoming a widespread group of drugs used both clinically and illicitly. The illicit use of AAS is diffused among adolescent and bodybuilders because of their anabolic proprieties and their capacity to increase tolerance to exercise. This systematic review aims to focus on side effects related to illicit AAS abuse, evaluating the scientific literature in order to underline the most frequent side effects on AAS abusers’ bodies. Materials and Methods: A systematic review of the scientific literature was performed using the PubMed database and the keywords “nandrolone decanoate”. The inclusion criteria for articles or abstracts were English language and the presence of the following words: “abuse” or “adverse effects”. After applying the exclusion and inclusion criteria, from a total of 766 articles, only 148 were considered eligible for the study. Results: The most reported adverse effects (found in more than 5% of the studies) were endocrine effects (18 studies, 42%), such as virilization, gynecomastia, hormonal disorders, dyslipidemia, genital alterations, and infertility; cardiovascular dysfunctions (six studies, 14%) such as vascular damage, coagulation disorders, and arteriosus hypertension; skin disorders (five studies, 12%) such as pricking, acne, and skin spots; psychiatric and mood disorders (four studies, 9%) such as aggressiveness, sleep disorders and anxiety; musculoskeletal disorders (two studies, 5%), excretory disorders (two studies, 5%), and gastrointestinal disorders (two studies, 5%). Conclusions: Based on the result of our study, the most common adverse effects secondary to the abuse of nandrolone decanoate (ND) involve the endocrine, cardiovascular, skin, and psychiatric systems. These data could prove useful to healthcare professionals in both sports and clinical settings.

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Section: Discussionmentioning

confidence: 99%

Nandrolone Decanoate: Use, Abuse and Side Effects

et al. 2020

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“…A full, accurate, and predictive model of IM ELQ-331 pharmacokinetics will be complex since it must include the rate of release of ELQ-331 from the injected oil depot; conversion to ELQ-300 by host esterases at the injection site, in lymph, blood, and in liver and other organs; absorption into blood; extensive protein binding in blood; distribution from blood to tissue; redistribution from tissue to blood; and elimination, with each component involving its own set of numerous variables [24, 33]. As a result, the absolute values of parameters estimated from simple compartmental PK analyses are unlikely to represent physiologic values in vivo, but the findings are powerful, nonetheless.…”

Section: Discussionmentioning

confidence: 99%

ELQ-331 as a prototype for extremely durable chemoprotection against malaria

Smilkstein

Pou

Krollenbrock

et al. 2019

Malar J

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Background The potential benefits of long-acting injectable chemoprotection (LAI-C) against malaria have been recently recognized, prompting a call for suitable candidate drugs to help meet this need. On the basis of its known pharmacodynamic and pharmacokinetic profiles after oral dosing, ELQ-331, a prodrug of the parasite mitochondrial electron transport inhibitor ELQ-300, was selected for study of pharmacokinetics and efficacy as LAI-C in mice. Methods Four trials were conducted in which mice were injected with a single intramuscular dose of ELQ-331 or other ELQ-300 prodrugs in sesame oil with 1.2% benzyl alcohol; the ELQ-300 content of the doses ranged from 2.5 to 30 mg/kg. Initial blood stage challenges with Plasmodium yoelii were used to establish the model, but the definitive study measure of efficacy was outcome after sporozoite challenge with a luciferase-expressing P. yoelii , assessed by whole-body live animal imaging. Snapshot determinations of plasma ELQ-300 concentration ([ELQ-300]) were made after all prodrug injections; after the highest dose of ELQ-331 (equivalent to 30 mg/kg ELQ-300), both [ELQ-331] and [ELQ-300] were measured at a series of timepoints from 6 h to 5½ months after injection. Results A single intramuscular injection of ELQ-331 outperformed four other ELQ-300 prodrugs and, at a dose equivalent to 30 mg/kg ELQ-300, protected mice against challenge with P. yoelii sporozoites for at least 4½ months. Pharmacokinetic evaluation revealed rapid and essentially complete conversion of ELQ-331 to ELQ-300, a rapidly achieved (< 6 h) and sustained (4–5 months) effective plasma ELQ-300 concentration, maximum ELQ-300 concentrations far below the estimated threshold for toxicity, and a distinctive ELQ-300 concentration versus time profile. Pharmacokinetic modeling indicates a high-capacity, slow-exchange tissue compartment which serves to accumulate and then slowly redistribute ELQ-300 into blood, and this property facilitates an extremely long period during which ELQ-300 concentration is sustained above a minimum fully-protective threshold (60–80 nM). Conclusions Extrapolation of these results to humans predicts that ELQ-331 should be capable of meeting and far-exceeding currently published duration-of-effect goals for anti-malarial LAI-C. Furthermore, the distinctive pharmacokinetic profile of ELQ-300 after treatment with ELQ-331 may facilitate durable protection and enable protection for far longer than 3 months. These findings suggest that ELQ-331 warrants consideration as a leading prototype for LAI-C.

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“…A full, accurate, and predictive model of IM ELQ-331 pharmacokinetics will be complex since it must include the rate of release of ELQ-331 from the injected oil depot; conversion to ELQ-300 by esterases at the injection site, in lymph, blood, and in liver and other organs; absorption into blood; extensive protein binding in blood; distribution from blood to tissue; redistribution from tissue to blood; and elimination, with each component involving its own set of numerous variables (24,31). As a result, the absolute values of parameters estimated from our simple compartmental PK analyses are unlikely to represent physiologic values in vivo, but the findings are powerful, nonetheless.…”

Section: Discussionmentioning

confidence: 99%

ELQ-331 as a prototype for extremely durable chemoprotection against malaria

Smilkstein

Pou

Krollenbrock

et al. 2019

Preprint

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Background:The potential benefits of long-acting injectable chemoprotection (LAI-C) against malaria have been recently recognized, prompting a call for suitable candidate drugs to help meet this need. On the basis of its known pharmacodynamic and pharmacokinetic profiles after oral dosing, ELQ-331, a prodrug of the parasite mitochondrial electron transport inhibitor ELQ-300, was selected for study of pharmacokinetics and efficacy as LAI-C in mice.Methods: Four trials were conducted in which mice were injected with a single intramuscular dose of ELQ-331 or other ELQ-300 prodrugs in sesame oil with 1.2% benzyl alcohol; the ELQ-300 content of the doses ranged from 2.5 to 30 mg/kg. Initial blood stage challenges with Plasmodium yoelii were used to establish the model, but the definitive study measure of efficacy was outcome after sporozoite challenge with a luciferase-expressing P.yoelii, assessed by whole-body live animal imaging. Snapshot determinations of plasma ELQ-300 concentration ([ELQ-300]) were made after all prodrug injections;after the highest dose of ELQ-331 (equivalent to 30 mg/kg ELQ-300), both [ELQ-331] and [ELQ-300] were measured at a series of timepoints from 6 hours to 5 ½ months after injection.

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Where does hydrolysis of nandrolone decanoate occur in the human body after release from an oil depot?

Cited by 13 publications

References 25 publications

Nandrolone Decanoate: Use, Abuse and Side Effects

Nandrolone Decanoate: Use, Abuse and Side Effects

ELQ-331 as a prototype for extremely durable chemoprotection against malaria

ELQ-331 as a prototype for extremely durable chemoprotection against malaria

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