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
A solution has a ratio strength of 1:10 000. You need 0.46 mg. Draw up the volume in the 10 mL syringe: what volume V is that?
1:10 0000.46 mg
V = mL
2.Pharmacy calculationsHard
A vial holds 500 mg of powder. You add 2.1 mL of diluent, and the powder adds 0.4 mL of volume. The prescription is 460 mg. Draw up the dose: what volume V do you give?
500 mg2.1 mL + 0.4 mL460 mg
V = mL
3.Dosage calculationsMedium
A child weighing 28 kg is prescribed 2 mg/kg of a drug. The stock solution contains 40 mg/mL. Draw up the dose: what volume V do you give?
28 kg2 mg/kg40 mg/mL
V = mL
4.Dosage calculationsHard
The prescription is 3300 units of a drug that comes as 10000 units/mL. Draw up the dose in the 1 mL syringe: what volume V do you give?
3300 units10000 units/mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 77 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.
77 kgVd = 7 L/kgC = 0.8 mcg/LF = 0.7
LD = mcg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). An 80 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?
80 kgVd = 0.5 L/kgC = 9 → 15 mg/LS = 0.8
LD = mg
3Solutions
1.Pharmacy calculations
Answer: V = 4.6 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.
Strength in mg/mL
1000 mg/10 000 mL = 0.1 mg/mL
Volume
V = 0.46/0.1 = 4.6 mL
Answer
V = 4.6 mL
2.Pharmacy calculations
Answer: V = 2.3 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
2.1 + 0.4 = 2.5 mL
C = 500/2.5 = 200 mg/mL
Volume
V = 460/200 = 2.3 mL
Answer
V = 2.3 mL
3.Dosage calculations
Answer: V = 1.4 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 = 2·28 = 56 mg
Volume
V = 56/40 = 1.4 mL
On the syringe
On this 10 mL syringe every small line is 0.2 mL.
Answer
V = 1.4 mL
4.Dosage calculations
Answer: V = 0.33 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.
Volume
V = 3300/10000 = 0.33 mL
On the syringe
On this 1 mL syringe every small line is 0.01 mL.
Answer
V = 0.33 mL
5.Clinical pharmacokinetics
Answer: LD = 616 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 = 7·77 = 539 L
Amount of active drug needed
Vd·C = 539·0.8 = 431.2 mcg
Loading dose
LD = 431.2/(1·0.7) = 616 mcg
Answer
LD = 616 mcg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: LD = 300 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 = 0.5·80 = 40 L
Rise needed
15 − 9 = 6 mg/L
Loading dose
LD = 40·6/(0.8·1) = 300 mg
Answer
LD = 300 mg
In practice the dose is rounded to a convenient amount.