Metabolic Drug-Drug Interaction Potential of Macrolactin A and 7-
            <i>O</i>
            -Succinyl Macrolactin A Assessed by Evaluating Cytochrome P450 Inhibition and Induction and UDP-Glucuronosyltransferase Inhibition
            <i>In Vitro</i>

Bae, Soo Hyeon; Kwon, Min Jo; Park, Jung Bae; Kim, Doyun; Kim, Dong‐Hee; Kang, Jian; Kim, Chun-Gyu; Oh, Euichaul; Bae, Soo Kyung

doi:10.1128/aac.00018-14

Cited by 12 publications

(11 citation statements)

References 34 publications

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“…For the experiments, O -desmethyltramadol HCl (M1), glucose 6-phosphate, glucose 6-phosphate dehydrogenase, MgCl 2 , β-nicotinamide adenine dinucleotide phosphate (NADP), chlorpropamide, Trizma ® base, Trizma ® hydrochloride, DMSO and formic acid were obtained from Sigma‒Aldrich (St. Louis, MO, USA). To evaluate the intrinsic clearance of M1 by CYPs, metabolic stability studies under NADPH system were conducted in human liver microsoms (HLM) [25,26]. For details, NADPH-generating system (1.3 mM NADP + , 3.3 mM glucose 6-phosphate, 3.3 mM MgCl 2 , and 0.4 unit/mL glucose-6-phosphate dehydrogenase) and HLM 0.25 mg/mL were added and preincubated at 37 °C for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O-Desmethyltramadol Pharmacokinetic Profiles in a Korean Population Using Physiologically-Based Pharmacokinetic Modeling

Jeong

Bae

et al. 2019

Pharmaceutics

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Tramadol is a μ-opioid receptor agonist and a monoamine reuptake inhibitor. O-desmethyltramadol (M1), the major active metabolite of tramadol, is produced by CYP2D6. A physiologically-based pharmacokinetic model was developed to predict changes in time-concentration profiles for tramadol and M1 according to dosage and CYP2D6 genotypes in the Korean population. Parallel artificial membrane permeation assay was performed to determine tramadol permeability, and the metabolic clearance of M1 was determined using human liver microsomes. Clinical study data were used to develop the model. Other physicochemical and pharmacokinetic parameters were obtained from the literature. Simulations for plasma concentrations of tramadol and M1 (after 100 mg tramadol was administered five times at 12-h intervals) were based on a total of 1000 virtual healthy Koreans using SimCYP® simulator. Geometric mean ratios (90% confidence intervals) (predicted/observed) for maximum plasma concentration at steady-state (Cmax,ss) and area under the curve at steady-state (AUClast,ss) were 0.79 (0.69–0.91) and 1.04 (0.85–1.28) for tramadol, and 0.63 (0.51–0.79) and 0.67 (0.54–0.84) for M1, respectively. The predicted time–concentration profiles of tramadol fitted well to observed profiles and those of M1 showed under-prediction. The developed model could be applied to predict concentration-dependent toxicities according to CYP2D6 genotypes and also, CYP2D6-related drug interactions.

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Section: Methodsmentioning

confidence: 99%

Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O-Desmethyltramadol Pharmacokinetic Profiles in a Korean Population Using Physiologically-Based Pharmacokinetic Modeling

Jeong

Bae

et al. 2019

Pharmaceutics

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“…Kang and colleagues recently demonstrated that the antiangiogenic activity of 48 relies on inhibition of class I phosphoinositide 3-kinases and subsequent signaling pathways. Additionally, Bae et al reported the inhibition of human liver cytochrome P450 isoform CYP2C9. The molecular basis of the antiviral and antibacterial properties of 48 remains largely unexplored to date.…”

Section: Macrolidesmentioning

confidence: 99%

Bioactive Secondary Metabolites from Bacillus subtilis: A Comprehensive Review

2019

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Bacillus subtilis is widely underappreciated for its inherent biosynthetic potential. This report comprehensively summarizes the known bioactive secondary metabolites from B. subtilis and highlights potential applications as plant pathogen control agents, drugs, and biosurfactants. B. subtilis is well known for the production of cyclic lipopeptides exhibiting strong surfactant and antimicrobial activities, such as surfactins, iturins, and fengycins. Several polyketide-derived macrolides as well as nonribosomal peptides, dihydroisocoumarins, and linear lipopeptides with antimicrobial properties have been reported, demonstrating the biosynthetic arsenal of this bacterium. Promising efforts toward the application of B. subtilis strains and their natural products in areas of agriculture and medicine are underway. However, industrial-scale availability of these compounds is currently limited by low fermentation yields and challenging accessibility via synthesis, necessitating the development of genetically engineered strains and optimized cultivation processes. We hope that this review will attract renewed interest in this often-overlooked bacterium and its impressive biosynthetic skill set.

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“…Currently, MA and SMA are being assessed in preclinical studies as antitumor and anti-macular degeneration agents at Daewoo Pharmaceutical Ind. Co., Ltd. (Gimhae, Korea) (33). Therefore, the present study investigated the possibility of utilizing SMA as new antitumor agent for glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

Antitumor activity of 7-O-succinyl macrolactin A tromethamine salt in the mouse glioma model

Choi¹,

Lee²,

Joo³

et al. 2017

Oncology Letters

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Abstract. Chemoradiotherapy with temozolomide is the current standard treatment option for patients with glioblastoma. However, the majority of patients with glioblastoma survive for <2 years. Therefore, it is necessary to develop more effective therapeutic strategies for the treatment of glioblastoma. 7-O-succinyl macrolactin A tromethamine salt (SMA salt), a macrolactin compound, is known to possess an antiangiogenic activity. The present study investigated the antitumor effects of SMA salt in the treatment of glioblastoma by evaluating in vitro and in vivo antitumor effects of SMA salt in an experimental glioblastoma model. The antitumor effects of the drug on human glioblastoma U87MG, U251MG and LN229 cell lines were assessed using in vitro cell viability, migration and invasion assays. Nude mice with established U87MG glioblastoma were assigned to either the control or SMA salt treatment group. The volume of tumors and the duration of survival were also measured. SMA salt affected cell viability and caused a concentration-dependent inhibition effect on the migration and invasion of glioblastoma cell lines. Animals in the SMA salt treatment group demonstrated a significant reduction in tumor volume and an increase in survival (P<0.05). Treatment with SMA salt presented more cytotoxic effects as well as anti-migration and anti-invasion activity compared with the control group in vitro and in vivo. These results suggest that SMA salt has significant antitumor effects on glioblastoma.

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Metabolic Drug-Drug Interaction Potential of Macrolactin A and 7- O -Succinyl Macrolactin A Assessed by Evaluating Cytochrome P450 Inhibition and Induction and UDP-Glucuronosyltransferase Inhibition In Vitro

Cited by 12 publications

References 34 publications

Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O-Desmethyltramadol Pharmacokinetic Profiles in a Korean Population Using Physiologically-Based Pharmacokinetic Modeling

Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O-Desmethyltramadol Pharmacokinetic Profiles in a Korean Population Using Physiologically-Based Pharmacokinetic Modeling

Bioactive Secondary Metabolites from Bacillus subtilis: A Comprehensive Review

Antitumor activity of 7-O-succinyl macrolactin A tromethamine salt in the mouse glioma model

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