Pick the relation: C = C₀·e−kt, LD = Vd·C/(S·F), maintenance rate = CL·Css/(S·F), τ = ln(Cpeak/Ctrough)/k.
For kidney function, estimate CrCl with Cockcroft–Gault first, then scale the dose or the interval.
Check the result: levels fall by half every half-life, and steady state takes about five half-lives.
2Practice problems
1.Pharmacy calculationsMedium
Practice exercise (made-up values, not clinical guidance). A vial contains ampicillin 500 mg as a powder. The practice label says to add 1.8 mL of sterile water; the powder adds 0.2 mL to the volume. The prescribed dose is 375 mg. What volume V do you draw up? Round to one decimal place.
500 mg1.8 mL+0.2 mL375 mg
V = mL
2.Pharmacy calculationsHard
A vial holds 250 mg of powder. You add 9.4 mL of diluent, and the powder adds 0.6 mL of volume. The prescription is 75 mg. Draw up the dose: what volume V do you give?
250 mg9.4 mL + 0.6 mL75 mg
V = mL
3.Dosage calculationsMedium
How many milligrams of drug m are in 20 mL of a 5% (w/v) solution?
5% w/v20 mL
m = mg
4.Dosage calculationsHard
The prescription is 390 micrograms. The ampoule contains 0.5 mg/mL. Draw up the dose in the 1 mL syringe: what volume V do you give?
390 mcg0.5 mg/mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 56 kg patient is to be loaded with digoxin tablets to reach a level of 0.8 mcg/L. The volume of distribution is 7 L/kg and the tablets have a bioavailability F = 0.7. Find the total oral loading dose LD in mcg.
56 kgVd = 7 L/kgC = 0.8 mcg/LF = 0.7
LD = mcg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 63 kg patient has a theophylline level of 9 mg/L; the target is 15 mg/L. The drug is given intravenously as aminophylline (S = 0.8), and the volume of distribution is 0.5 L/kg. What extra loading dose LD raises the level to the target?
63 kgVd = 0.5 L/kgC = 9 → 15 mg/LS = 0.8
LD = mg
3Solutions
1.Pharmacy calculations
Answer: V = 1.5 mL
Reconstitution: the powder takes up space, so the final volume is the diluent plus the powder volume. Concentration = drug in the vial/final volume, and the volume to give = dose/concentration. On a multi-strength label, use the concentration that belongs to the amount of diluent you actually added. The numbers are for practice only; at the bedside always follow local protocols and have high-risk doses double-checked.
Final volume
1.8 + 0.2 = 2 mL
Concentration
500/2 = 250 mg/mL
Volume to give
V = 375/250 = 1.5 mL
Answer
V = 1.5 mL
2.Pharmacy calculations
Answer: V = 3 mL
Strength to volume: turn the strength into mg per mL first. A w/v percentage is grams per 100 mL, so x% = 10x mg/mL. A ratio strength 1:n is 1 g in n mL. After reconstitution the concentration is the powder's dose over the final volume (diluent + powder volume). Then volume = dose/concentration.
Final volume and concentration
9.4 + 0.6 = 10 mL
C = 250/10 = 25 mg/mL
Volume
V = 75/25 = 3 mL
Answer
V = 3 mL
3.Dosage calculations
Answer: m = 1000 mg
Solution strengths: a percentage strength is grams per 100 mL, so 1% = 1 g/100 mL = 10 mg/mL. A ratio strength 1:1000 means 1 g in 1000 mL = 1 mg/mL; 1:10 000 is 0.1 mg/mL. For a dilution the amount of drug stays the same: C₁·V₁ = C₂·V₂.
Concentration
5% = 5 g/100 mL = 50 mg/mL
Mass of drug
m = 50·20 = 1000 mg
Answer
m = 1000 mg
4.Dosage calculations
Answer: V = 0.78 mL
Drawing up a dose: volume = (prescribed dose/stock strength) × stock volume. Convert to the same units first, then check that the volume fits the syringe and lands on one of its graduations.
Same units
0.5 mg/mL = 500 mcg/mL
Volume
V = 390/500 = 0.78 mL
Answer
V = 0.78 mL
5.Clinical pharmacokinetics
Answer: LD = 448 mcg
Clearance and volume: at steady state the dosing rate equals the elimination rate, so the maintenance rate = CL × Css. A loading dose is LD = Vd × C/(S × F), with S the salt factor (fraction of active drug in the salt) and F the bioavailability (1 for IV). From two levels, k = ln(C₁/C₂)/Δt; for an IV bolus Vd = dose/C₀ and CL = k × Vd. The numbers are for practice only; at the bedside always follow local protocols and have high-risk doses double-checked.
Volume of distribution
Vd = 7·56 = 392 L
Amount of active drug needed
Vd·C = 392·0.8 = 313.6 mcg
Loading dose
LD = 313.6/(1·0.7) = 448 mcg
Answer
LD = 448 mcg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: LD = 236.3 mg
Designing a regimen: with rapid IV doses the level falls from peak to trough during the interval, so τ = ln(Cpeak/Ctrough)/k and the dose that restores the peak is Vd × (Cpeak − Ctrough). The average steady-state level is Css,avg = S·F·dose/(CL·τ). An infusion rises as C = (R/CL)(1 − e−kt). For a drug cleared by the kidneys, the dose is scaled with the creatinine clearance. The numbers are for practice only; at the bedside always follow local protocols and have high-risk doses double-checked.
Volume of distribution
Vd = 0.5·63 = 31.5 L
Rise needed
15 − 9 = 6 mg/L
Loading dose
LD = 31.5·6/(0.8·1) = 236.3 mg
Answer
LD = 236.3 mg
In practice the dose is rounded to a convenient amount.