China
Africa
Explore chapters and articles related to this topic
Understanding Brain Delivery
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Joana Bicker, Ana Fortuna, Gilberto Alves, Amílcar Falcäo
Pregnancy has been associated with an increase of BBB permeability as a result of hemodynamic changes in the brain. It does not appear to be related with differences of tight junction expression but with a higher hydrostatic pressure on the BBB [99]. The main adaptations of cerebral circulation and BBB to pregnancy were described by Cipolla et al. [100] and include the protective role which the BBB exerts against peripherally activated leucocytes, microglia and tumour necrosis factor alpha (TNF-α), which could provoke neuronal hyperexcitability and seizures in pregnant women. In addition, there are a few studies concerning potential alterations in foetal BBB related to efflux transporters. Viral infections during pregnancy [101] and short-term exposure to sertraline (4 h) [102] resulted in P-gp inhibition in foetal and maternal BBB. In opposition, placental P-gp was activated after sertraline exposure, suggesting a tissue-specific effect [102]. This tissue-specific effect has also been observed for norbuprenorphine, a P-gp substrate. P-gp had a minor role in its foetal exposure but highly restricted its brain distribution [103]. On the other hand, chronic exposure to zidovudine induced BCRP expression in both foetal brain and placenta [104].
Critical care, neurology and analgesia
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Buprenorphine is a partial μ-agonist with 30–50 times the potency of morphine [204]. Buprenorphine shows slow receptor association (30 min), but with high affinity to multiple sites from which dissociation is very slow (Teq =166 min) and incomplete (50% binding after 1 h) [204]. Peak effect may not occur until 3 h and duration of effect in adults is prolonged (<10 h). High doses of naloxone are required to antagonise buprenorphine because of its relative inability to displace buprenorphine from opioid receptors [200,205]. Buprenorphine’s metabolite, norbuprenorphine, has dose-dependent analgesic activity and efficacy similar to its parent [206].
Information on level of drugs into breastmilk
Published in Wendy Jones, Breastfeeding and Medication, 2018
Ilett KF, Hackett LP, Gower S, Doherty DA, Hamilton D, Bartu AE, Estimated dose exposure of the neonate to buprenorphine and its metabolite norbuprenorphine via breastmilk during maternal buprenorphine substitution treatment, Breastfeed Med, 2012;7:269–74.
Respiratory depression following medications for opioid use disorder (MOUD)-approved buprenorphine product oral exposures; National Poison Database System 2003–2019
Published in Clinical Toxicology, 2021
Michael A. Darracq, Stephen L. Thornton
We speculate that these observations and the lack of sufficient explanatory variables by logistic regression reflect other as of yet unidentified factors that increase the likelihood of respiratory depression in those orally exposed to buprenorphine. One potential explanation that has not been fully evaluated in the medical literature is variability in cytochrome P450 activity in the metabolism of buprenorphine. Buprenorphine is metabolized via N-demethylation by cytochrome P450(CYP) 3A4 to norbuprenorphine, a potent and full opioid receptor agonist that has recently been implicated in causing respiratory depression both in animal and human studies [16–19]. Previously reported fatal cases of buprenorphine overdose demonstrated very high plasma or tissue concentrations of norbuprenorphine [20–22]. Because CYP3A4 demonstrates considerable activity variability in the population, it is possible that some potential recipients of buprenorphine may have a pharmacogenomic predisposition to adverse effects including respiratory depression or more serious medical outcomes [23].
A narrative review of buprenorphine in adult cancer pain
Published in Expert Review of Clinical Pharmacology, 2020
Matthew Degnan, Shaker A. Mousa
Buprenorphine is extensively metabolized to norbuprenorphine through CYP3A4, and its glucuronidation results in two metabolites having very little activity and that are mainly excreted through feces and minimally excreted through the kidneys [18]. Norbuprenorphine is a full agonist but has low blood brain barrier permeability and is subject to P-glycoprotein efflux. Although it has limited oral bioavailability due to hepatic first-pass metabolism, it has good lipophilicity and mediocre water solubility, allowing it to be administered through a variety of routes. These alternative routes bypass the extensive first-pass metabolism by the liver and, as a result, can reduce the variability of plasma concentrations [6,21]. TD formulations are especially unique due to their ability to maintain a constant plasma concentration [21]. TD formulations can also be useful when oral administration is not possible, such as in gastrointestinal cancers, head and neck cancers, or when there is severe nausea and vomiting. SL and TD buprenorphine were found to have potencies of about 80 times and 100 times stronger, respectively, than morphine [22].
Buprenorphine treatment for opioid use disorder: recent progress
Published in Expert Review of Clinical Pharmacology, 2019
Suprit Parida, Kathleen M. Carroll, Ismene L. Petrakis, Mehmet Sofuoglu
Due to extensive first-past metabolism, the bioavailability of oral BUP is 10–15%. The SL tablet and buccal formulations have better bioavailability than oral BUP, 12–33% and 46–65%, respectively [47]. Following SL administration, peak levels of BUP are reached within 30 to 60 min and the plasma elimination half-life of BUP is about 30 h [47]. In contrast, the elimination half-life after IV administration is about 3 h. This discrepancy between the SL and oral routes is likely due to sequestration of SL BUP in oral mucosa and fat tissue. BUP is metabolized primarily by glucuronidation to BUP glucuronide and cytochrome P450 3A4-mediated N-dealkylation to its active metabolite, norbuprenorphine. Although norbuprenorphine is a potent MOR agonist, it has poor CNS penetration and may not contribute to the pharmacological effects of BUP [48]. Urine test for norbuprenorphine helps to ensure that the individual is taking BUP and not simply adding BUP to the urine sample.