Commonly Used Excipients Modulate UDP-Glucuronosyltransferase 2B7 Activity to Improve Nalbuphine Oral Bioavailability in Humans

Wang, Hong Jaan; Hsiong, Cheng Huei; Ho, Shung Tai; Lin, Mei; Shih, Tiffany Ting-Fang; Huang, Pei Wei; Hu, Oliver Yoa Pu

doi:10.1007/s11095-013-1272-4

Cited by 17 publications

(10 citation statements)

References 34 publications

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“…Pain is a negative factor that seriously affects a patient's postoperative recovery. Surgical trauma can activate peripheral and visceral nociceptors ( 8 ) to induce central pain sensory nerve sensitization and peripheral sensory nerve conduction enhancement ( 9 ), leading to a decreased threshold for those receptors and an over-threshold response enhancement, which is called hyperalgesia ( 10 ). At the same time, tissue damage caused by surgical trauma can further lead to the generation and aggregation of inflammatory mediators and pain-related factors, further aggravating pain ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Nalbuphine for analgesia after fracture surgery and its effect on circulating inflammatory factors

2017

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The present study evaluated the use of nalbuphine for analgesia after fraction reduction surgery. Eighty lower limb fracture patients needing open reduction and internal fixation were selected in the First People's Hospital of Jingzhou from January 2015 to December 2015. Patients were randomly divided into observation and control groups (with 40 cases in each). After surgery, the patients in the observation group were treated with nalbuphine (2 mg/kg) for patient-controlled intravenous analgesia (PCIA), while sufentanil (2.5 µg/kg) was used for patients in the control group. The analgesia treatment lasted for 48 h after surgery. Changes in inflammatory factors and catecholamine hormones during the observation period were determined and compared between the groups. Pain, sedation scores and the number of times the analgesia pump was used were recorded at different time-points. Additionally, the life and sleep qualities and any adverse reactions were also recorded. Our results showed that after the operation, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), high-sensitivity CRP (hs-CRP) cortisol, adrenaline epinephrine (AD) and norepinephrine (NE) were significantly lower in the observation group than in the control group (P<0.05). Pain and sedation scores of patients in the observation group were better than those in the control group at all time-points after operation (P<0.05). Life and sleep qualities of patients in the observation group were also better than those in the control group (P<0.05). Finally, the rates of nausea, vomiting, dizziness, lethargy, urinary retention, skin itch and constipation were significantly lower in the observation group than in control group (P<0.05). Based on our findings, the application of nalbuphine for analgesia in patients with fracture surgeries can reduce the levels of inflammatory cytokines, improve the analgesic effect, bring beneficial sedative effects and reduce the occurrence of adverse reactions.

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Section: Discussionmentioning

confidence: 99%

Nalbuphine for analgesia after fracture surgery and its effect on circulating inflammatory factors

2017

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“…[28][29][30] It is metabolized by UGT2B7 and not cytochrome P450 oxidation and hence has few drug interactions. 31 The area under the curve of nalbuphine plasma concentrations increases 85% in renal failure, so doses need to be reduced. Although it has been safely given to those who are dialysis dependent.…”

Section: Nalbuphinementioning

confidence: 99%

What Parenteral Opioids to Use in Face of Shortages of Morphine, Hydromorphone, and Fentanyl

Davis

McPherson

Mehta

et al. 2018

Am J Hosp Palliat Care

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“…The innovative point of our research is to reveal the interaction between PEG400 and UGT1A family members (UGT1A8 and UGT1A9), which is different from previous studies. 31 Unfortunately, we have not been able to explain the mechanism by which PEG400 interacts with transport enzymes and metabolic enzymes. In the system of solution containing PEG400, the process of metabolism and transportation of B is changed.…”

Section: Ta B L E 3 Kinetic Parameters Of Baicalein Glucuronidation B...mentioning

confidence: 99%

The pharmaceutical excipient PEG400 affect the absorption of baicalein in Caco‐2 monolayer model by interacting with UDP‐glucuronosyltransferases and efflux transport proteins

Cao

Zhang

Yuan

et al. 2022

Pharmacology Res & Perspec

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The bioavailability of drugs is often related to intestinal metabolism and transport mechanisms. In previous studies, pharmaceutical excipients were recognized as inert substances in clinical safety evaluations. However, a large number of studies have shown that pharmaceutical excipients regulate the metabolism and transport of drugs in the body and improve the bioavailability. The pharmaceutical excipient polyethylene glycol 400 (PEG400) as a good solubilizer and surfactant has the potential to improve the bioavailability of drugs. The combined action of UDP‐glucuronosyltransferases (UGTs) and efflux transport proteins is responsible for the intestinal disposition and poor bioavailability of baicalein. Our aim is to study the effect of PEG400 on the absorption of baicalein on the Caco‐2 monolayer, and confirm the interaction of PEG400 with UGTs (UGT1A8 and UGT1A9) and efflux transports. We initially found that baicalein in the Caco‐2 monolayer would be metabolized into glucuronide conjugates BG and B6G under the action of UGT1A8 and UGT1A9 on the endoplasmic reticulum membrane, and then mainly excreted to different sides by acting of MRP and BCRP. The addition of PEG400 significantly accelerated the metabolism of B in Caco‐2 cells and increased the penetration of BG and B6G. Furthermore, PEG400 also significantly decreased the efflux ratio of BG and B6G, which was the evidence of the interaction with the efflux transporters. In the in vitro intestinal microsome regeneration system, low concentration PEG400 decreased the Km value of UGT1A8 and UGT1A9 (key enzymes that mediate the production of BG and B6G); high concentration PEG400 enhanced the Vmax value of UGT1A8 and UGT1A9. In conclusion, our results determined that PEG400 interacted with some UGTs and efflux transporters, which were the main factors affecting the absorption of baicalein.

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Commonly Used Excipients Modulate UDP-Glucuronosyltransferase 2B7 Activity to Improve Nalbuphine Oral Bioavailability in Humans

Abstract: Tween-PEG successfully improved oral NAL bioavailability and could formulate a useful oral dosage form for patient's convenience.

Cited by 17 publications

References 34 publications

Nalbuphine for analgesia after fracture surgery and its effect on circulating inflammatory factors

Nalbuphine for analgesia after fracture surgery and its effect on circulating inflammatory factors

What Parenteral Opioids to Use in Face of Shortages of Morphine, Hydromorphone, and Fentanyl

The pharmaceutical excipient PEG400 affect the absorption of baicalein in Caco‐2 monolayer model by interacting with UDP‐glucuronosyltransferases and efflux transport proteins

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