(Total Views: 313)
Posted On: 12/01/2025 12:38:08 PM
Post# of 158771
I posted two relevant excerpts from that paper a while back
Though one got deleted. Even though the info the paper hinted at was kind of unknown if paying close attn.
First
"Moreover, maraviroc displays relatively low oral bioavailability, largely attributable to extensive first-pass hepatic metabolism, which complicates dose optimization and contributes to interindividual variability in systemic exposure [229]. An additional limitation is its reduced permeability across the BBB. Although maraviroc exerts immunomodulatory effects in peripheral tissues, its constrained CNS penetration raises concerns regarding adequate engagement of CCR5 within spinal and supraspinal regions that mediate pain processing, where CCR5-driven neuroinflammatory cascades are central to the onset and development of neuropathic pain [230]. Consequently, attaining therapeutically meaningful CCR5 inhibition in the CNS with maraviroc might require elevated systemic exposure, thus increasing the risk of hepatotoxicity and unfavorable pharmacokinetic interactions"...
Second
.."Monoclonal antibodies directed against CCR5, including leronlimab (PRO-140), have been tested in clinical populations like HIV-1, oncology, and COVID-19 [232,233,234]. These studies confirm sustained receptor occupancy, predictable pharmacokinetics, and a favorable safety profile. Although no neuropathic pain-specific clinical data are currently available, the immunomodulatory actions of leronlimab align well with mechanistic pathways implicated in neuroinflammatory pain. The long-lasting therapeutic effect and receptor interaction of monoclonal antibodies could be helpful in chronic pain diseases requiring suppression of immune-neuronal signaling"...
Though one got deleted. Even though the info the paper hinted at was kind of unknown if paying close attn.
First
"Moreover, maraviroc displays relatively low oral bioavailability, largely attributable to extensive first-pass hepatic metabolism, which complicates dose optimization and contributes to interindividual variability in systemic exposure [229]. An additional limitation is its reduced permeability across the BBB. Although maraviroc exerts immunomodulatory effects in peripheral tissues, its constrained CNS penetration raises concerns regarding adequate engagement of CCR5 within spinal and supraspinal regions that mediate pain processing, where CCR5-driven neuroinflammatory cascades are central to the onset and development of neuropathic pain [230]. Consequently, attaining therapeutically meaningful CCR5 inhibition in the CNS with maraviroc might require elevated systemic exposure, thus increasing the risk of hepatotoxicity and unfavorable pharmacokinetic interactions"...
Second
.."Monoclonal antibodies directed against CCR5, including leronlimab (PRO-140), have been tested in clinical populations like HIV-1, oncology, and COVID-19 [232,233,234]. These studies confirm sustained receptor occupancy, predictable pharmacokinetics, and a favorable safety profile. Although no neuropathic pain-specific clinical data are currently available, the immunomodulatory actions of leronlimab align well with mechanistic pathways implicated in neuroinflammatory pain. The long-lasting therapeutic effect and receptor interaction of monoclonal antibodies could be helpful in chronic pain diseases requiring suppression of immune-neuronal signaling"...
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