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 0.22 mg. Draw up the volume in the 10 mL syringe: what volume V is that?
1:10 0000.22 mg
V = mL
2.Pharmacy calculationsHard
A vial holds 2000 mg of powder. You add 9.8 mL of diluent, and the powder adds 0.2 mL of volume. The prescription is 480 mg. Draw up the dose: what volume V do you give?
2000 mg9.8 mL + 0.2 mL480 mg
V = mL
3.Dosage calculationsMedium
A patient weighing 101 kg has a body surface area of 1.9 m². The prescription is 20 mg/m². Find the dose D in mg.
101 kgBSA = 1.9 m²20 mg/m²
D = mg
4.Dosage calculationsHard
A child weighing 10 kg is prescribed 12.5 mg/kg per dose of an oral suspension that contains 120 mg in 5 mL. What volume V do you give? Round to one decimal place.
10 kg12.5 mg/kg120 mg/5 mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 54 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.
54 kgVd = 7 L/kgC = 0.8 mcg/LF = 0.7
LD = mcg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). An 82-year-old woman weighs 71 kg and has a serum creatinine of 1.9 mg/dL (168 µmol/L). Estimate the creatinine clearance with Cockcroft–Gault: CrCl (mL/min) = (140 − age) × weight (kg)/(72 × SCr in mg/dL), × 0.85 for women. The usual digoxin dose is 250 mcg for a creatinine clearance of 100 mL/min, and a fraction fe = 0.7 of the drug is excreted unchanged by the kidneys. Using the Dettli dose fraction Q = 1 − fe·(1 − CrCl/normal CrCl), find the adjusted dose D. Round to the nearest whole number.
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 = 0.22/0.1 = 2.2 mL
Answer
V = 2.2 mL
2.Pharmacy calculations
Answer: V = 2.4 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
9.8 + 0.2 = 10 mL
C = 2000/10 = 200 mg/mL
Volume
V = 480/200 = 2.4 mL
Answer
V = 2.4 mL
3.Dosage calculations
Answer: D = 38 mg
Body-surface-area dosing: many cytotoxic and some paediatric doses are prescribed per square metre of body surface area: dose (mg) = dose per m² × BSA (m²). The Mosteller formula estimates BSA = √(height (cm) × weight (kg)/3600).
Dose
D = 20·1.9 = 38 mg
Answer
D = 38 mg
4.Dosage calculations
Answer: V = 5.2 mL
Dose calculation: the amount to give equals what is prescribed divided by what you have, times the quantity it comes in: amount = (desired dose/stock strength) × stock volume. Always keep the units the same (convert g to mg, mg to mcg first) and check that the answer is sensible.
Dose from weight
12.5·10 = 125 mg
Volume
V = (125/120)·5 = 5.208 ≈ 5.2 mL
Answer
V = 5.2 mL
5.Clinical pharmacokinetics
Answer: LD = 432 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 = 7·54 = 378 L
Amount of active drug needed
Vd·C = 378·0.8 = 302.4 mcg
Loading dose
LD = 302.4/(1·0.7) = 432 mcg
Answer
LD = 432 mcg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: D = 120 mcg
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.
Creatinine clearance (Cockcroft–Gault)
CrCl = (140 − 82)·71/(72·1.9)·0.85 = 25.59 mL/min
Dose fraction (Dettli)
Q = 1 − 0.7·(1 − 25.59/100) = 0.4791
Adjusted dose
D = 0.4791·250 = 119.8 ≈ 120 mcg
Answer
D = 120 mcg
In practice the dose is rounded to a convenient amount and checked against the product information.