A patient has been on the antibiotic ampicillin for some time (E. coli upper urinary tract infection; this would not be the correct therapy - i.e. one would not use ampicillin alone, and pl. ignore this point here). He now is stable enough to be switched to a drug that has the same mechanism of action and antibacterial spectrum, but it is commonly used orally.
The infusion rate of ampicillin was 500 mg/kg/day.
You make the switch on day zero at 8 am, stopping ampicillin infusion and starting with amoxicillin oral 4 times a day.
How much amoxicillin should you give orally every 4 hours, and how long would it take for the switch to be complete, i.e. the patient being on full therapy with amoxicillin? The half life of ampicillin is about 1 hour.
Each hour you lose 21 mg of ampicillin (500mg/24 hrs), and you would have lost 168 mg (21^4=168) in 4 hours.According to " what goes out mist come in" rule, 168mg of amoxicillin should be given every 4 hours also (half life of amoxicillin is same as ampicillin =61.3 min).
ReplyDeleteIt would take about 4-6 hours(4 half -lives) to complete the switch because the principle of reaching steady state is always retained.
Is it right....?
I think your whole concept of what is lost must be put back in is the way to approach this but your math is off. You didn't calc the amount of ampicillin that was lost the right way.
ReplyDeleteThe is a first order exponential decay... thus:
A = A_0 x e ^-(kt)
In this case K can be calculated by taking 0.693 and dividing by the half-life (in this case 1 h)
We are solving for A (new concentration) and A_0 is the initially concentration (500mL/kg) and t = 4 hours
Solving we get the new concentration is 31.25 remaining. Therefore, you have to subtract this from the initially concentration to see how much was lost. (which would be 467.85)
Or more logically put:
Hour 0 = 500 mg
Hour 1 = 500/2 = 250
Hour 2= 250/2 = 125
Hour 3 = 125/2 = 62.5
Hour 4 = 62.5/2 = 31.25 Remaining (Therefore 500 - 31.25 = 467.85 was lost)
I think there is a little confusion here. The 500 mg/kg/day (a 70kg individual receives a drip at ~24mg/min) is the infusion rate, which would compensate for losses if it were steady state. To me 500 mg/kg/day seems like a fairly high dose.
ReplyDeleteBased on a quick PubMed search the pharmokinetics gave a value of 4.76mL/min/kg as the clearance, so concentration would be about 73 mg/L:
500mg/kg/day = 0.35 mg/kg/min
0.35mg/kg/min is cleared at a rate of 4.76 mL/min/kg
0.35 / 4.76 = 0.07 mg/mL or ~73 mg/L
73mg/L is what I think would be your steady state plasma concentration.
As far as oral amoxacillin dosing, I am not sure how to go about it. But is the regiment 4 hours or 4 times a day, or is it early dosing to load up?
Also, since the half-life is 1 hour and dosing is 4 hours, the ampicillin & amoxacillin would be around 6.25% before even taking the second dose of amoxacillin, so either you load them or overall levels of circulating lactam will decline.