The pharmacokinetics and bioavailability of mebendazole in man: a pilot study using [3H]‐mebendazole.

Dawson, Michael J.; Allan, Richard; Watson, T. R.

doi:10.1111/j.1365-2125.1982.tb02008.x

Cited by 33 publications

(16 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results of this tracer dose study in patients with a history of cystic hydatid disease compare favourably with those obtained from a pilot study (Dawson et al, 1982), in a young healthy volunteer.…”

Section: Discussionsupporting

confidence: 59%

“…We have now formulated a solution of radiolabelled mebendazole and have utilized this solution to further define the pharmacokinetics of the drug in terms of bioavailability, half-life and extent of first pass effect following intravenous and oral administration, initially by a pilot study in a single volunteer (Dawson et al, 1982) and now to a group of volunteers in separate studies 5 days apart.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The pharmacokinetics and bioavailability of a tracer dose of [3H]‐ mebendazole in man.

Dawson¹,

Braithwaite²,

Roberts³

et al. 1985

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

1 Five volunteers, whose ages ranged between 37 and 64 years, took part in a crossover study to determine the pharmacokinetics and bioavailability of mebendazole in man following intravenous and oral administration of a tracer dose of [3H]-mebendazole. 2 Following intravenous administration, the average distribution half-life, elimination half-life and rate of clearance were 0.20 h, 1.12 h, and 1.063 min respectively. 3 After oral administration of the solution, the average elimination half-life was 0.93 h, the apparent rate of clearance was 0.846 /min, the average time to peak plasma concentration was 0.42 h, and the bioavailability of mebendazole was 22%. 4 Comparison of metabolite area under the plasma concentration vs time data from each route of administration indicates that absorption of mebendazole from the gastrointestinal tract at this dose level is almost complete. The low bioavailability observed following oral administration at this dose level is postulated to be due to high first pass elimination. 5 Approximately half of the administered dose of radioactivity following intravenous and oral administration was detected in the urine, and the major unconjugated metabolite of mebendazole was found to be 2-amino-5(6) [ot-hydroxybenzyl]benzimidazole (IV), not 2-amino-5(6)benzoylbenzimidazole (II), as previously reported.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

The pharmacokinetics and bioavailability of a tracer dose of [3H]‐ mebendazole in man.

Dawson¹,

Braithwaite²,

Roberts³

et al. 1985

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mebendazole has poor bioavailability: following oral administration, approximately 17–20% of the dose reaches the systemic circulation [19,20] due to the fact of incomplete absorption and extensive first-pass effect. Great inter-individual variation in pharmacokinetics have been reported [21,22,23,24,25] (Table 1) after administration for helminthic infections and in healthy volunteers.…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature

Guerini

Triggiani

Maddalo

et al. 2019

Cancers

113

View full text Add to dashboard Cite

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called “cancer stem cells”. Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.

show abstract

“…Comparison of the metabolite areas under the plasma concentration-time profile from each route of administration indicated that absorption of the compound from the gastrointestinal tract was close to 100%, but exhibited high first-pass elimination. 12,13 Simulation Methodology…”

Section: Compound Physicochemical Properties and Backgroundmentioning

confidence: 99%

Food Effect Projections via Physiologically Based Pharmacokinetic Modeling: Predictive Case Studies

Tistaert

Heimbach

Xia³

et al. 2019

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Food can alter the absorption of orally administered drugs. Biopharmaceutics physiologically based pharmacokinetic (PBPK) modeling offers the possibility to simulate a compound's pharmacokinetics under fasted or fed states. To advance the utility of PBPK modeling, with a view to regulatory impact, we have pooled our experience across 4 pharmaceutical companies to propose a general multistep PBPK workflow leveraging pre-existing clinical data for immediate-release formulations of Biopharmaceutics Classification System I and II compounds. With this strategy, we wish to promote pragmatic PBPK approaches for compounds where absorption is well understood, that is, compounds with moderate-to-high permeability that are not substrates for uptake transporters. Five case studies demonstrate how food effect can be well predicted using appropriately established and validated models. The case studies integrate solubility and dissolution data for initial model development and apply a "middle-out" validation with clinical data in one prandial state. Then, whenever possible, a validation against both fasted and fed state data is recommended before application of the models prospectively for to-be-marketed formulations. Thus, when combined with limited clinical data, PBPK models could be used to simulate outcomes for new doses, formulations, or active pharmaceutical ingredient forms, in lieu of a clinical food-effect study.

show abstract

The pharmacokinetics and bioavailability of mebendazole in man: a pilot study using [3H]‐mebendazole.

Cited by 33 publications

References 6 publications

The pharmacokinetics and bioavailability of a tracer dose of [3H]‐ mebendazole in man.

The pharmacokinetics and bioavailability of a tracer dose of [3H]‐ mebendazole in man.

Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature

Food Effect Projections via Physiologically Based Pharmacokinetic Modeling: Predictive Case Studies

Contact Info

Product

Resources

About