My question was based on your statement above of 15-mg BID several posts back. Now, should the dose be 15 mg BID or 150 mg BID? I’m not sure, but it seems to me that I saw somewhere in a RapAdmin post on Maraviroc that 15 mg BID or 30 mg daily would be appropriate.
Yes, I think it was 30mg but I’d cut 150 into four pieces and do it once per day to start and then maybe go twice per day. I wouldn’t go more than 75mg daily.
Have you ever tried LDN 3mg-4.5mg. A lot of people seem to have good results with it. I use it and it is an excellent medication for aches and pains (but never had covid so can’t speak to that). Maybe worth a shot.
I’ve been exploring dosing approaches to try and replicate the effects from the mouse studies. The behavior of maraviroc in humans vs. mice is so different, a compounded micro dose may be needed. For now the approach I’m going with is to split 150 mg tablet into quarters (37.5 mg) and dose every 2 weeks. Here’s the analysis of that approach from Grok:
Dosing Interval to Approximate Mouse Study Approach
To address your question directly: yes, dosing frequency should ideally be based on the ratio of duration of inhibition to no inhibition to maintain a similar proportion of time under CCR5 inhibition, as this could better replicate the “pulsed” exposure profile in mouse studies where transient, short-lived inhibition (followed by extended troughs) led to senotherapeutic effects like reduced senescence and improved muscle/memory outcomes. However, this ratio must be adjusted for species differences in physiology (e.g., metabolism, half-life, and aging time scales) to ensure biological relevance—direct ratio matching without scaling could result in overly extended intervals that may not align with human senescence dynamics.
Mouse Exposure Profile Recap
In key studies (e.g., 2025 senescence/sarcopenia models), mice received 10 mg/kg IP every 2 days (48-hour interval).
Mouse half-life ~0.9 hours leads to rapid clearance: peak concentrations (~3600 ng/mL) drop below thresholds for meaningful inhibition (>30% occupancy, requiring ~793 ng/mL due to low mouse CCR5 affinity) within ~2 hours.
Thus, ~2 hours of inhibition followed by ~46 hours of no inhibition per cycle (ratio 1:23, or ~4% time under inhibition).
This pulsed profile (short bursts with long recovery) is thought to drive the “hit-and-run” senolytic-like effects without constant blockade.
Human Exposure Profile for Low Dose (37.5 mg Oral)
A single 37.5 mg oral dose achieves peak concentrations ~17-28 ng/mL (scaled from 225 ng/mL for 300 mg single dose, adjusted for non-proportional PK and lower bioavailability ~20-23% at <100 mg).
Human half-life ~14-18 hours (mean 16 hours) and high CCR5 affinity (KD ~0.089 ng/mL for 50% occupancy) result in prolonged high occupancy: >95% at peak, sustained >30% (threshold ~0.038 ng/mL) for ~5-6 days (time to drop from Cmax to threshold ~141 hours post-peak, approximating total duration above threshold).
This creates a much longer inhibition phase than in mice, even at minimal doses.
Recommended Dosing Interval: Every 2 Weeks (Scaling the Ratio with Allometric Considerations)
Direct Ratio Matching: To preserve the mouse 1:23 ratio (inhibition:no-inhibition), human no-inhibition would be ~115-138 days for a 5-6 day inhibition duration, yielding an interval of ~120-144 days (every 4-5 months). However, this ignores slower human metabolism and aging processes, potentially leading to insufficient pulses over time for cumulative senotherapeutic benefits.
Adjusted with Allometric Scaling for Time/Frequency: Pharmacological translation often scales time intervals (e.g., dosing frequency, half-life effects) by body weight^0.25 (~7-8 for mouse [0.025 kg] to human [70 kg]), as this accounts for metabolic rate differences and better predicts human PK/PD from animal data. Scaling the mouse 48-hour interval by ~7-8 gives ~14-16 days in humans.
This maintains a scaled ratio: Human inhibition ~5-6 days (mouse 2 hours * ~18x half-life ratio, but capped by allometric ~7-8x), no-inhibition ~9-10 days (mouse 46 hours *7-8), ratio ~1:1.8 (adjusted from 1:23 to reflect faster mouse biology).
Result: ~35-40% time under inhibition per cycle (higher than mouse’s ~4%), but biologically appropriate for slower human senescence turnover.
