LGD-4033 + RAD-140 (8 weeks)

LGD-4033 trial oral preparation, fasted. Oral. healthy men age 21–50;1 mg PKcohortn 14 onday 1.

LGD-4033 parent: estimated concentration in plasma (ng/mL).

30 his midpoint ofpublished 24–36 h;3 happroximate first-dose peak fromoriginal Figure 1.

Calibration dose

1 mg

Reported calibration peak

5 ng/mL

Peak timing used

3 hours

Terminal half-life used

30 hours

Reconstructed absorption rate

1.38839 /hour

• Already embodied in observed exposure; do not multiply by an extra F.
• Dose scaling and repeated-dose superposition use fixed parameters; the example dose does not calibrate the curve.
• One-compartment AUC~232 is close to repeated-dose 238 under linear steady-state identity, but predicted peak accumulation~2.4 is below observed~3.
• Day 1 shows secondary 24–48 h peaks; single Bateman cannot reproduce them.
• Human repeated-dose range maxed 1 mg/day;5 mg and above is extrapolation.
• No extra 60% bioavailability; mass unit conversion 100 ng/dL=1 ng/mL.
• The first-dose peak is read approximately from the source figure, and 30 h is the midpoint of its 24–36 h terminal range.
• The model predicts a day-21 peak about 11.9 ng/mL versus about 16 in the source figure and misses secondary peaks, despite AUC being within about 2.6%.

• Basaria et al 2013 LGD-4033 phase 1

  0.1/0.3/1 mg,20 dosesover 21 days; day 2 omitted; h 24–36, AUCday 21=19/85/238 ng·h/m L; near 3×accumulation.

• Basaria Figure 1

  Top 1 mgbluecurve peaksabout 5 ng/mL at 3 h; late 24–48 h secondary plateau; bottomday 21 peakabout 16 ng/mL.

Estimate ligandrol-source-estimate-2026-10 · version 1

Limited oncology-study terminal estimate;6 hwasnot universal Tmax.

One 1 mg input peaks at 1 relative unit after a single dose. Other amounts scale proportionally; overlapping doses add when accumulation is on. Different compounds use separate relative scales.

Timing half-life used

44.7 hours

Absorption half-life assumed

11.175 hours

Reference amount for the relative scale

1 mg

• Absorption half-life is assumed to be one quarter of the slower timescale (11.175 h); it is not a measured absorption parameter.
• A single 1-unit input has a peak of 1 relative unit; scaling and repeated-dose addition are mathematical assumptions. This normalization is independent of the example dose.
• No adequate single Bateman kernel from one patient terminal rate and multiple peaks.
• 10 mg extrapolation cannot be presented as measured healthy male PK.
• Doping microdose urine concentrations are not blood Cmax.

• Lo Russo et al 2022 first-in-human RAD 140

  22 postmenopausal women with advanced breast cancer;50/100/150 mg,100 mg PK expansion.

• Public mirror of Lo Russo original preproof

  100 mgsingle:Cmax 447 ng/mL, AUC 0–24=7044, AUClast 32981; latepeaks; h 44.7 reliable in one patient.

testolone-relative-timing-2026-10 · version 1