Escalating past the approved maximum, examined honestly
Higher doses of these molecules have been studied. In general they produced modest additional efficacy and disproportionate additional symptom burden, which is why the…
Priya Ramanathan, PharmD
Page 3 of 7 of this archive, newest first.
Archive — page 3
131 piecesThe supply gap as a clinical event
Why the reason for stopping changes what happens afterwards.
What a 1 mL syringe does that a 0.3 mL syringe does not
A unit is a volume. A dose is a mass. The bridge between them is concentration, and concentration is a number somebody has to calculate.
The steps get smaller as the ladder gets higher, and that is deliberate
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
Gauge, pain and flow rate
Skin thickness at the standard injection sites is approximately two millimetres in adults and varies remarkably little with body mass. That single finding is why short…
How a correct calculation becomes a wrong dose
Almost every case involves a change — a new vial, a new syringe size, a new supplier — carried forward with an old number.
Escalating onto a rising curve
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
The mechanism behind the mechanism
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
The mechanism behind the mechanism
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
Vitamin D, adiposity, and a volume-of-distribution problem
Reduced intake is a plausible mechanism for deficiency. Reduced absorption is not, and the two are conflated in most of the advice.
The mechanism behind the mechanism
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
From milligrams in a vial to units in a barrel
A more concentrated reconstitution means smaller injection volumes, which means larger proportional errors from graduation, dead space and technique.
The mechanism behind the mechanism
Delayed gastric emptying is a mechanism that becomes an adverse effect above a threshold. It is not a complication in the ordinary sense.
The lowest effective dose is a real concept with almost no data behind it
Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced one — has not been randomised.
Do you need the top of the ladder?
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
Vagal afferents, the area postrema, and the anatomy of nausea
A tour of the tissues where the receptor is expressed, and what happens in each.
The GLP-1 receptor is not a switch, and survodutide is not a key
What the in-vitro data supports, what it does not, and where the extrapolation to a person begins.
The incretin receptors, ranked by how much we actually know about them
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
Why purity is the cheapest number to flatter
The Journal has read several hundred certificates from twenty companies. The number is almost always there; the method behind it almost never is.