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Posted On: 11/01/2024 9:23:29 AM
Post# of 147996
Re: KenChowder #147673
I had a thought to complete the RECOVER form but will have to wait till the weekend when I can do it properly and backed up with references. I am familiar with pharmacokinetics as it relates to drug dosing of aminoglycoside class drugs such as gentamicin, tobramycin and amikacin but these involve serologic drug levels where sampling amounts to a simple blood draw and you are trying to calculate drug peak and trough levels factoring in a bunch of variables like drug dose, kidney function, volume of distribution of drug etc…I don’t think of kinetics in the cerebral compartment so much…you don’t just go sampling brain tissue outside of animal research and sampling from CSF still requires access that is only done for better reasons than kinetics. I think most longs are aware and have heard Leronlimab crosses the blood brain barrier with about 70% CCR5 receptor occupancy. This is fantastic news that it crosses at all, as the implication for brain tumors like glioblastoma become apparent…along with Alzheimer’s, but also the brain fog etc associated with long COVID. I think that comment we’ve heard from Scott Kelly et al from Cytodyn may have come from this reference involving rhesus macaques:
https://journals.plos.org/plospathogens/artic...at.1010396
“Because ARVs tissue distribution is heterogenous [23,24], we investigated the degree of tissue penetrance by Leronlimab. During euthanasia at week 15, saline was perfused into Leronlimab-treated macaques to remove peripheral blood from tissues to allow for the assessment of tissue-resident Leronlimab. We detected a wide range of concentrations from all sampled tissues, and concomitantly measured near-complete CCR5 RO by Leronlimab in non-brain tissues. Leronlimab CCR5 RO in brain tissues was ~70%, with the lowest tissue concentration of all sampled tissues found in brain (Fig 4A, 4B, 4C and S5 Table). ”
https://journals.plos.org/plospathogens/artic...at.1010396
“Because ARVs tissue distribution is heterogenous [23,24], we investigated the degree of tissue penetrance by Leronlimab. During euthanasia at week 15, saline was perfused into Leronlimab-treated macaques to remove peripheral blood from tissues to allow for the assessment of tissue-resident Leronlimab. We detected a wide range of concentrations from all sampled tissues, and concomitantly measured near-complete CCR5 RO by Leronlimab in non-brain tissues. Leronlimab CCR5 RO in brain tissues was ~70%, with the lowest tissue concentration of all sampled tissues found in brain (Fig 4A, 4B, 4C and S5 Table). ”
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