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 ceftriaxone 1000 mg as a powder. The practice label says to add 9.6 mL of sterile water; the powder adds 0.4 mL to the volume. The prescribed dose is 750 mg. What volume V do you draw up? Round to one decimal place.
1000 mg9.6 mL+0.4 mL750 mg
V = mL
2.Pharmacy calculationsHard
A vial holds 250 mg of powder. You add 1.9 mL of diluent, and the powder adds 0.6 mL of volume. The prescription is 180 mg. Draw up the dose: what volume V do you give?
250 mg1.9 mL + 0.6 mL180 mg
V = mL
3.Dosage calculationsMedium
A child weighing 15 kg is prescribed 20 mg/kg of a drug. The stock solution contains 50 mg/mL. Draw up the dose: what volume V do you give?
15 kg20 mg/kg50 mg/mL
V = mL
4.Dosage calculationsHard
You must prepare 250 mL of a 2.5% (w/v) solution from a 10% (w/v) stock solution. What volume of stock V₁ do you need?
C₁ = 10%C₂ = 2.5%V₂ = 250 mL
V₁ = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). An 83 kg patient is to be loaded intravenously with phenytoin sodium to reach a phenytoin level of 15 mg/L. The volume of distribution is 0.7 L/kg and the salt factor is S = 0.92. Find the loading dose LD of phenytoin sodium in mg.
83 kgVd = 0.7 L/kgC = 15 mg/LS = 0.92
LD = mg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A patient's tobramycin half-life is 3 h. The target is a peak of 8 mg/L and a trough of 1 mg/L. Assuming rapid IV doses and first-order elimination, what dosing interval τ lets the level fall from the peak to the trough? Round to one decimal place.
t½ = 3 hCpeak = 8 mg/LCtrough = 1 mg/L
τ = h
3Solutions
1.Pharmacy calculations
Answer: V = 7.5 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
9.6 + 0.4 = 10 mL
Concentration
1000/10 = 100 mg/mL
Volume to give
V = 750/100 = 7.5 mL
Answer
V = 7.5 mL
2.Pharmacy calculations
Answer: V = 1.8 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
1.9 + 0.6 = 2.5 mL
C = 250/2.5 = 100 mg/mL
Volume
V = 180/100 = 1.8 mL
Answer
V = 1.8 mL
3.Dosage calculations
Answer: V = 6 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.
Dose from body weight
D = 20·15 = 300 mg
Volume
V = 300/50 = 6 mL
On the syringe
On this 10 mL syringe every small line is 0.2 mL.
Answer
V = 6 mL
4.Dosage calculations
Answer: V₁ = 62.5 mL
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.
Volume of stock
V₁ = 2.5·250/10 = 62.5 mL
Answer
V₁ = 62.5 mL
5.Clinical pharmacokinetics
Answer: LD = 947.3 mg
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 = 0.7·83 = 58.1 L
Amount of active drug needed
Vd·C = 58.1·15 = 871.5 mg
Loading dose
LD = 871.5/(0.92·1) = 947.3 mg
Answer
LD = 947.3 mg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: τ = 9 h
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.
Rate constant
k = 0.693/3 = 0.231 h⁻¹
Dosing interval
τ = ln(8/1)/0.231 = 2.079/0.231 = 9 h
Answer
τ = 9 h
In practice the interval is rounded to a convenient value such as 8, 12, 24 or 36 h, and the levels are checked again.