Disposition of [14C]γ-Cyclodextrin in Germ-Free and Conventional Rats

Bie, A.T.H.J. De; Ommen, Ben van; Bär, A.

doi:10.1006/rtph.1998.1219

Cited by 48 publications

(31 citation statements)

References 15 publications

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“…So, on average, 95% of the radioactivity detected in the urine could be attributed to sugammadex, as analyzed by LC-MS, suggesting there was very limited, if any, metabolism of sugammadex. 14 Moreover, the cumulative amount of radioactivity excreted in either feces or exhaled air was <0.02% in all patients.…”

Section: Safety and Tolerabilitymentioning

confidence: 79%

“…A total of six subjects were selected because this number is generally considered adequate for studies evaluating the disposition of 14 C-labeled compounds. The study protocol was approved by an independent ethics committee (Stichting Beoordeling Ethiek BioMedisch Onderzoek, Assen, The Netherlands) and was conducted in compliance with the Declaration of Helsinki, the International Conference on Harmonization Guidelines, Good Clinical Practice, and current regulatory requirements.…”

Section: Methodsmentioning

confidence: 99%

“…bolus dose of 14 C-labeled sugammadex at a therapeutic dose level of 4 mg/kg (with 0.025 MBq/kg bodyweight of 14 C-radioactivity, about 1.85 MBq per subject); the radiolabel was located on each of the side chains ( Figure 1). Study drug administration was performed on the morning of day 1, after an overnight fast of at least 10 h. The use of any concomitant prescription or nonprescription drug (with the exception of intermittent paracetamol) was prohibited during the entire treatment period (i.e.…”

Section: Study Drug Administrationmentioning

confidence: 99%

“…Despite this relatively high urinary recovery of sugammadex, quantified by tandem liquid chromatography mass spectrometry (LC-MS), a minor role of metabolism in the clearance of sugammadex cannot be excluded. The use of 14 Clabeled sugammadex enables determination of the extent of metabolism and the relative contribution of the various routes of excretion to elimination.…”

Section: Introductionmentioning

confidence: 99%

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Sugammadex is cleared rapidly and primarily unchanged via renal excretion

Peeters

Passier

Smeets

et al. 2011

Biopharm & Drug Disp

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Sugammadex is a modified γ‐cyclodextrin which rapidly reverses rocuronium‐and vecuronium‐induced neuromuscular blockade. Previous studies suggest that sugammadex is mostly excreted unchanged via the kidneys. This single‐center, open‐label, non‐randomized study used 14C‐labeled sugammadex to further investigate the excretion, metabolic and pharmacokinetic (PK) profiles of sugammadex in six healthy male volunteers. 14C‐labeled sugammadex 4 mg/kg (0.025 MBq/kg of 14C‐radioactivity) was administered as a single intravenous bolus. Blood, urine, feces and exhaled air samples were collected at pre‐defined intervals for assessment of sugammadex by liquid chromatography‐mass spectrometry (LC‐MS) and for radioactivity measurements. Adverse events were also assessed. Excretion of sugammadex was rapid with ∼70% of the dose excreted within 6 h and ∼90% within 24 h. Less than 0.02% of radioactivity was excreted in feces or exhaled air. Ninety‐five percent of the radioactivity detected in urine could be attributed to sugammadex, as determined by LC‐MS, suggesting very limited metabolism of sugammadex. LC‐MS analysis of plasma samples found that sugammadex accounted for 100% of total 14C‐radioactivity in the plasma. In general, PK parameters determined from radioactivity and sugammadex plasma concentrations were very similar. Any adverse events were of mild‐to‐moderate intensity, and judged unrelated to sugammadex. These findings demonstrate that sugammadex is cleared rapidly, almost exclusively via the kidney, with minimal or no metabolism. Copyright © 2011 John Wiley & Sons, Ltd.

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Section: Safety and Tolerabilitymentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Study Drug Administrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sugammadex is cleared rapidly and primarily unchanged via renal excretion

Peeters

Passier

Smeets

et al. 2011

Biopharm & Drug Disp

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“…[47] γ-CD has low bioavailability because it cannot permeate through the biological membranes easily and digested rapidly in the gastrointestinal tract and also excreted through the urine in unchanged form after parental administration. [56][57][58][59][60] High water solubility, larger cavity size, and most favorable toxicological profile make the γ-CD a better candidate to enhance the properties of drugs. [42] Recently, Saokham and Loftsson presented a detailed summary of γ-CD about formulation, physicochemical properties, toxicological profile, and applications in different areas.…”

Section: β-Cyclodextrin (β-Cd)mentioning

confidence: 99%

Untitled

Budhwar¹

2018

AJP

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Inclusion complexes have various applications in different fields of drug delivery and pharmaceutical industry due to their ability of complexation with guest molecules and enhancement of the physicochemical properties of guest molecules. Cyclodextrins and their derivatives have the ability to encapsulate the bioactive compounds into its cavity and protect these from the environmental conditions, improve the solubility, bioavailability, and other properties also. The aim of this review is to highlight the advantages of cyclodextrins in the enhancement of physicochemical properties of drugs (such as solubility, stability, bioavailability, permeability, and others), different methods for production and various characterization techniques used for evaluation of complexes. Applications of cyclodextrin complexes in pharmaceutical and other fields are also explained here with examples. Thus cyclodextrins, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems accompanied with the delivery of different novel drugs through various delivery routes.

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