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Dose-proportionality versus dose-linearity [PK / PD]

posted by ElMaestro - Denmark, 2018-08-03 11:21  - Posting: # 19132
Views: 1,507

(edited by ElMaestro on 2018-08-03 11:43)

[2006, at an EU agency, in a meeting room on the 4th floor.....]

Chairman: " it looks like we are done with the agenda. I'd like to thank all of you for attending. Minutes from this meeting will be circulated first to you and then to the committee within 30 days. Unless there are more questions I'd like to wrap up this meeting, and I expect to see you all again in three months."
(Silent room... 1 second... 2 seconds.... someone raises a finger)
Chairman: "Yes, Romain?"
Romain: "I have just a little outstanding topic that I feel we must address."
Chairman: "Oh for fucks sa..., I mean: Romain, please go ahead."
Romain: "It concerns the distinction between pharmacokinetic linearity and pharmacokinetic proportionality, a matter which I am sure you all agree has to be a top priority because we are entrusted to work on only the most serious matters."
The chairman closes his eyes and bangs his head into the table.
Jerome: "Dang, there goes my flight home."
Melissa: "Haven't we wasted...I mean spent... about 5000 hours discussing this during the last 4 meetings?!"
Romain: "If you don't agree with me then it is because you don't understand. Didn't you read the 87 papers I sent you before this meeting? Villeroy & Boch clearly showed in 1967 that..."
Aaron: "Dear God, please wake me up from this nightmare."
Chairman, eyes still closed: "Since it is past 3:30pm the agency's staff are no longer at work. You will need to sort out your own hotels and flights."
Romain: "We need to do something!"
Chairman, slowly opening his eyes, now a distinctly new look on his face: "You are absolutely right, Romain. You are absolutely right."
A leftover tomato from the lunch cart smashes into Romain's forehead. Kathi throws a handbag into his face. Someone pokes Romain in the left eye with chopsticks. 16 people closing in on Romain. Then sheer mayhem. A flurry of punches flying through the air, along with a few chairs. Eyeglasses, socks and a laptop charger go airborne. A bit of blood spatter here and there.
Melissa: "Ewww Romain, this shirt was all white, now it has matrix all over it, you filthy fucking bastard."
Someone's dentures hitting the wall. The sound of a knee cap busting due to its sudden encounter with a baseball bat. A high-heeled shoe hammers into the projector in the ceiling. It crashes down on top of the chairman's head. Electric sparks, then a lot of smoke and the smell of burned scalp.

3 floors below, at the Department of Access Control and Safety. A bright orange light suddenly flashing on a dashboard. An alarm goes off.
Goon 1: "Oh... looks like we have another code red on the fourth floor."
Goon 2: "What's happening there?"
Goon 1: "Someone apparently mentioned linearity."
Goon 2: "Oh shit. Not again. Last time it took 15 people an hour to separate them."
Goon 1, smiling: "Not to mention the cleanup afterwards.... but hey, it's past 3:30pm."
Goon 2: "Nothing we can do, then. The overtime budget got exhausted two months ago."
Goon 2 reaches under the dashboard and disconnects a wire. The bright orange light disappears. The alarm stops.

[And so forth...]

if (3) 4

Best regards,

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.

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