Theory 68/Timing & Gating/Pharmacology
Toxicity Is Gated by the Clock
The claim
The toxicity of a drug is set by the phase of administration relative to the target tissue's circadian cycle, not by dose alone.
01Mechanism
Drug-metabolising enzymes and transporters oscillate; the same concentration encounters different machinery depending on when it arrives.
02Prediction
Toxicity should vary with administration time at equal dose.
03Refutation
Toxicity independent of timing would remove the gate.