Drug Metabolism

Uetrecht, Jack; Trager, William

doi:10.3109/9780849375965

Cited by 12 publications

(1 citation statement)

References 54 publications

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“…Our violet-laser pointer is intensive enough to produce bright figures that can be observed in a classroom without needing to black out the room. However, lasers in class 3R (power output below 5 mW for wavelengths in the 400-700-nm range) might be potentially hazardous to the eyes [2,3]. The laser in this class (3R) should therefore be treated with care; looking directly into the laser beam must be avoided.…”

Section: Discussionmentioning

confidence: 99%

Lissajous figures drawn by a Blackburn pendulum on phosphorescent foil

Navrátil¹,

Poláček²

2013

Phys. Educ.

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Section: Discussionmentioning

confidence: 99%

Lissajous figures drawn by a Blackburn pendulum on phosphorescent foil

Navrátil¹,

Poláček²

2013

Phys. Educ.

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Affinity purification, identification, and biochemical characterization of Gamma-glutamyl transpeptidase, a membrane anchored enzyme of Gigantocotyle explanatum

et al. 2023

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Gamma-glutamyl Transpeptidase is an enzyme that facilitates the transfer of glutamyl groups from glutamyl peptides to other peptides or water. Additionally, it also participates in important processes such amino acid transport, cellular redox control, drug detoxi cation, apoptosis, and DNA fragmentation in a various organism. In the present study, GGT activity in Gigantocotyle explanatum was examined in order to characterize the enzyme in the helminth system. GGT is isolated using membrane solubilization and puri ed through a nity column chromatography (Con-A Sepharose column). Km and Vmax values, as well as the optimal pH, optimal temperature, and incubation period, are also determined using enzyme kinetics. The hetero-dimeric property of the enzyme is demonstrated by the puri ed GGT, which yielded two subunits of 65.5 and 55 kDa. The optimal pH and temperature are found to be 8.0 and 37°C, respectively. While assessing the optimal incubation time of the enzyme, it was observed that the puri ed GGT not only retained its functional integrity up to 15 min but also re ected considerable thermostability at higher temperatures, by retaining 78% and 25% of its initial activities at 50°C and 60°C, respectively. 1 mM concentration of 6-Diazo-5-Oxo Nor-isoleucine (DON), a speci c inhibitor of GGT, completely abolished GGT activity. These results suggest that GGT in these worms is a catalytically active enzyme with distinguishing characteristics that can be used for further study to comprehend its function in amphistome biology and in host-parasite relationships, especially since the potential therapeutic candidacy of the GGT enzyme has already been indicated in these groups of organisms.

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Improving the oral bioavailability of tapentadol via a carbamate prodrug approach: synthesis, bioactivation, and pharmacokinetics

Wang

Zhang

et al. 2018

Drug Deliv. and Transl. Res.

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Tapentadol suffers from rapid clearance due to extensive metabolism in vivo, which results in low oral bioavailability. In the present study, three novel prodrugs of tapentadol (WWJ01, WWJ02, and WWJ03) were synthesized to improve its metabolic stability and thereby improve its oral bioavailability. They all exhibited good stability in phosphate buffers, simulated gastrointestinal fluids, rat plasma, and intestinal and liver homogenates. Disappointingly, the N,N-diethylcarbamate prodrug of tapentadol (WWJ02) and the N,N-diisopropylcarbamate prodrug of tapentadol (WWJ03) were metabolized into inactive metabolites when incubated with liver microsomes. In contrast, the N,N-dimethylcarbamate prodrug of tapentadol (WWJ01) could be transformed into useful intermediates (M1, M2, and M3), followed by the further release of the active structure (tapentadol) with the addition of plasma. Additionally, the possible biotransformation pathway of WWJ01 was preliminarily studied with a qualitative approach by determining the molecular weight and fragment ions of its metabolic intermediates. Finally, pharmacokinetic studies were carried out to evaluate the oral absorption of WWJ01. WWJ01 showed distinct advantages in oral absorption efficiency, with a 2.3-fold higher bioavailability than tapentadol. These results suggest that the rational design of a carbamate prodrug of tapentadol is an efficient strategy to improve its metabolic stability and oral bioavailability.

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Drug Metabolism

Cited by 12 publications

References 54 publications

Lissajous figures drawn by a Blackburn pendulum on phosphorescent foil

Lissajous figures drawn by a Blackburn pendulum on phosphorescent foil

Affinity purification, identification, and biochemical characterization of Gamma-glutamyl transpeptidase, a membrane anchored enzyme of Gigantocotyle explanatum

Improving the oral bioavailability of tapentadol via a carbamate prodrug approach: synthesis, bioactivation, and pharmacokinetics

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