Calculations Flashcards
Define glomerular filtration rate
Rate of formation of filtrate. Volume/Time
Define clearance
The volume of plasma from which the substance is completely removed/cleared in a unit of time (volume/time)
Largest source of error in a clearance measurement?
Accuracy of timed urine collection (using mL implies an unrealistic degree of accuracy - L to 2 sig figs would be better)
Define tubular reabsorption (TR)
Proportion (fraction) of filtered substance that is reabsorbed. By definition, TR = 1-FE
Cockroft Gault equation
Creatinine clearance (mL/min) = [(140-age) x Body wt (kg) x 1.3]/plasma creatinine (umol/L)
Multiply by 0.85 for women (to correct for muscle mass)
Least significant change equation
2.77 x CV (including assay and within subject variation)
Bioavailability
dose reaching circulation / dose administered
Salt conversion factor
MW free (parent) drug / MW drug administered (salt of the drug)
Bioavailability taking into account salt conversion factor
Dose of drug reaching circulation / (salt conversion factor x dose of drug administered)
Volume of distribution
amount of drug in body / plasma concentration
Clearance of a drug
Cl (r) + Cl (m) where Cl(r) = renal clearance and Cl(m) = hepatic metabolism
In practice, hepatic metabolism hard to quantify and most dosage calcs take into account impairment of renal fn only
What is first order kinetics?
When the rate of drug clearance changes in proportion to the remaining drug concentration in plasma. Rate decreases as concentration decreases. Exponential decay.
What is zero order kinetics?
When the rate of drug clearance is constant and independent of plasma drug concentration. Inverse linear relationship between drug concentration and time.
What is k(d)?
The elimination rate constant.
decrease in plasma concentration of drug / unit time is proportional to plasma concentration
The elimination rate constant is a proportionality constant introduced such that the above relationship can be written:
decrease in plasma concentration of drug / unit time = k(d) x Cp(t)
ie decrease in plasma concentration of drug / Cp(t) = k(d) x d(t)
where Cp(t) = plasma concentration of drug at any point in time
What is e and what is its approximate value?
e = a universal constant encountered in nature whenever we are dealing with exponential growth or decay.
Approximately equal to 2.718
What equation is used to find concentration at time, t, if we know concentration at time, 0 and the elimination rate constant, for a drug that follows first order kinetics?
ln Cp(t) = ln Cp(0) - k(d).t
Express the elimination rate constant in terms of half lives of a drug
k(d) = 0.693 or ln2 divided by t(1/2)
where t(1/2) = half life of the drug
If we know the half life of a drug, t(1/2) and it’s initial concentration, Cp(0), what equation can we use to determine the plasma concentration at time, t?
Substitute for k(d):
lnCp(t) = lnCp(0) - 0.693/t(1/2) x t
OR
lnCp(t) = lnCp(0) - 0.693t/t(1/2)
Rate of elimination, R(E), of a drug?
Amount of drug removed per unit time
R(E) = clearance x plasma concentration at steady state, Cp(ss)
Rate of administration, R(A), of a drug?
Dose x salt conversion factor x bioavailability (amount that reaches plasma) / interval between doses (tau)
How do rate of elimination and rate of administration compare when a drug is at steady state?
R(A) = R(E)
T or F: For a drug that is eliminated by glomerular filtration alone, clearance = GFR
True
How can k(d) be expressed using clearance and volume of distribution?
k(d) = Cl/V(d)
The fraction of total body drug eliminated from the body per unit time
ie R(E) / amount of drug in body
ie [Cl x Cp(ss)] / [V(d) x Cp(ss)]
Cp(ss) term cancels, leaving Cl/V(d)
Composition of body fluids
- TBW = 60% body wt
- ECF = 20% body wt
- plasma = 1/4 ECF (5% body wt)
