Here’s some additional estimates for lower doses: 75 mg QD
Timepoint
CSF range (ng/mL)
Equilibrium RO
Effective RO*
Peak (~2h)
2.3 – 4.2
96 – 98%
~97 – 99%
Average
0.40 – 0.73
82 – 89%
~87 – 92%
Trough (24h)
0.07 – 0.14
44 – 61%
~60 – 75%
37.5 mg QD
Timepoint
CSF range (ng/mL)
Equilibrium RO
Effective RO*
Peak (~2h)
1.0 – 1.9
92 – 96%
~94 – 97%
Average
0.18 – 0.33
67 – 79%
~75 – 84%
Trough (24h)
0.03 – 0.06
25 – 40%
~45 – 55%
Interpretation Against Neurological Benefit Thresholds
Metric
75 mg QD
37.5 mg QD
Target
Peak RO
97–99%
94–97%
Both excellent
Average RO
87–92%
75–84%
Both likely above anti-inflammatory threshold (~70–80%)
Trough RO
60–75%
45–55%
75 mg: marginal; 37.5 mg: below anti-inflammatory, borderline for plasticity
Hours/day >80% RO
~18–20h
~12–16h
—
Hours/day >50% RO
~22–24h
~18–21h
—
Bottom line
75 mg QD sits in an interesting zone. Peak and average RO are robust — well above plausible anti-inflammatory thresholds. The vulnerability is the trough. At 60–75% effective RO, you’re above the CCR5Δ32-heterozygote analogue (~50%) but potentially below sustained leukocyte trafficking inhibition. For plasticity/cognitive enhancement (the CREB/MAPK pathway story from Joy et al.), 75 mg QD likely delivers meaningful benefit for most of the day. For chronic neuroinflammation suppression, the ~4–6 hours per day spent below 80% RO may matter depending on how rapidly inflammatory signaling re-establishes when CCR5 becomes partially available.
37.5 mg QD is the dose where the model starts breaking down in your favor. The trough at 45–55% effective RO means CCR5 is functionally “half-open” for several hours overnight. Average RO of 75–84% puts you in the lower bound of anti-inflammatory benefit. This dose might still provide meaningful plasticity enhancement (CCR5Δ32 heterozygote analogy — ~50% functional block correlates with improved stroke outcomes), but it’s hard to argue for robust anti-neuroinflammatory coverage.
Claude has a good caveat that answer’s your question: “No human data exist at these doses for any endpoint. The lowest clinically tested dose for non-HIV neurological benefit is 150 mg/day (MARCH trial low-dose arm). Everything below that is uncharted.”
Generally with anything hepatic, both acute and cumulative dose matters. Less will be less stress. Anyone taking Maraviroc needs to be testing their hepatic enzymes.
Thanks @fasterfour (and Claude) for the detailed analysis. I’m wondering if it makes sense to take a higher dose than 37.5, say 150 mg once or twice a week. Thoughts?
Sure, there’s lots of possible dosing regimes that could be effective. What’s likely needed depends on what benefit you are targeting. Relative dosing targets - sarcopenia < CNS plasticity (memory) < CNS anti-inflammation. I think reasonable dosing ranges from 37.5mg every other week to 150 mg/day. I would suggest starting conservatively, test hepatic enzymes, and slowly increase dose as long you aren’t getting elevated hepatic enzyme levels. Along the way, test different regimes that have equivalent cumulative dosing to see if one is better than the other.
@fasterfour I put the request in for my doc. I’m sure he’ll tell me also, but do you think the one month mark is a good time to retest hepatic enzymes, or?? Ty
To further clarify, if the justification for weekly or biweekly pulse dosing to prevent sarcopenia is based on a translation of murine chronobiology to human chronobiology, should we apply the same logic to dementia prevention dosing? Here, some of the research is also on middle-aged mice, although ongoing human trials are BID or QD. What do the half-life and other pharmacokinetics suggest?