While calculating the appropriate dose of vancomycin
for a given patient from creatinine clearance sounds good, it's not
always practical. It would be more effective if vancomycin were
eliminated solely via renal excretion; but vancomycin doesn't often
cooperate so nicely. Metabolism and excretion also involve hepatic
metabolism, biliary and fecal excretion, and a few other more-esoteric
factors, all to what amount to largely unpredictable extents. Those
extents seem to depend upon individually-variable parameters whose
measurement is not yet a viable science. Three patients with the same
CrCl can have substantially different rates of elimination.
Thus, creatinine clearance can be a useful tool in estimating an
initial dosing regimen; but peak and trough levels have proven
more practical as ongoing dosing parameters. A variety of nomograms have
been developed for dosing, and any level of complex calculations can be
employed to devise appropriate dosing regimens. It's nice to know how
to do all that, and such intricacies have their place; but astrophysics
are rarely essential when throwing darts across the room. Since
elimination often evades simple calculation, successful dosing
can generally be more intuitive by relying on experience with a few
basic tenets. For most patients, a few very simple rules that economize
on time and effort can be both safe and effective:
1. Begin dosing according to creatinine clearance: * CrCl > 60 - start with 1gm q12h or 10-20mg/Kg/dose q12h * CrCl 40-60 - start with 10-20mg/Kg/dose q24h * CrCl <40 - Think 5mg/Kg/dose (or less for more severe impairment) and/or q36-48h, even q72hours.
2. Dose at convenient intervals for simplicity: q6hours q8hours q12hours q18hours q24hours q36hours q48hours q72hours
3. Dose with standardized amounts of drug: 250mg 500mg 750mg 1gm 1250mg 1500mg 2gm
4. Adjust doses by changing schedule, amount of drug administered, or both.
5. Once peak and trough values are available, adjustment is simplified. Therapeutic values are considered: Peak 20-40mcg/ml Trough 5-15mcg/ml * Some clinicians deem trough values to be sufficient for proper adjustment. Peaks usually fall into line accordingly.
6. Dosing efficacy depends upon accuracy of peak and trough values, which depend upon accurate timing. *Trough is measured immediately before dosing. *Peak is usually measured 1 hour following completion of administration. *Deviation
from those times can substantially affect accuracy of results; and
while adjustments can be made mathematically for deviations (and knowing
EXACTLY by how much times have been fudged), everyone is better-off by
sticking to that strict schedule.
7.
Low-tech adjustments can be made by educated guesswork. A slightly-low
trough (over 6, but less than 10) will usually respond appropriately by
either increasing dose size by one increment (Rule 3 above), or
decreasing dosing interval by one increment (Rule 2 above). Successful
therapy depends upon attaining and maintaining therapeutic blood
levels, but toxicity must be avoided by not exceeding recommended
maximum peak and trough values. Realize that
increasing dose from 1gm to 1250mg on a bid regimen increases daily dose
by 500mg; while keeping the same dose of 1gm and decreasing the dosing
interval from 12 hours to 8 hours increases daily dose by 1gm, producing
a greater change in peak and trough. Levels
higher than desired are reduced in the same manner, with either larger
dose reductions or increases in dosing interval required for larger
excesses. Changing both dosing parameters produces much greater changes. More complex processes will be discussed in further reading.
