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 cefuroxime 750 mg as a powder. The practice label says to add 7.2 mL of sterile water; the powder adds 0.3 mL to the volume. The prescribed dose is 225 mg. What volume V do you draw up? Round to one decimal place.
750 mg7.2 mL+0.3 mL225 mg
V = mL
2.Pharmacy calculationsHard
Practice exercise (made-up values, not clinical guidance). You must prepare 300 mL of 30% dextrose by mixing 50% and 10% dextrose. How many mL V of the 50% solution do you need? Round to the nearest whole mL.
50%10%30%300 mL
V = mL
3.Dosage calculationsMedium
A vial contains 2 g of powder. The label says: add 7.4 mL of water for injection to give a total volume of 8 mL. The prescription is 100 mg. What volume V of the reconstituted solution do you give?
2 g+ 7.4 mL → 8 mL100 mg
V = mL
4.Dosage calculationsHard
A child weighing 28 kg is prescribed 5 mg/kg per dose of an oral suspension that contains 125 mg in 5 mL. What volume V do you give?
28 kg5 mg/kg125 mg/5 mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 69 kg patient is to be loaded intravenously with phenytoin sodium to reach a phenytoin level of 20 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.
69 kgVd = 0.7 L/kgC = 20 mg/LS = 0.92
LD = mg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 58-year-old man weighs 82 kg and has a serum creatinine of 1.4 mg/dL (124 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 tobramycin regimen is 120 mg every 8 h for a creatinine clearance of 120 mL/min. Keeping the dose, the interval is lengthened in proportion to the fall in clearance. Find the new dosing interval τ. Round to one decimal place.
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
7.2 + 0.3 = 7.5 mL
Concentration
750/7.5 = 100 mg/mL
Volume to give
V = 225/100 = 2.25 ≈ 2.3 mL
Answer
V = 2.3 mL
2.Pharmacy calculations
Answer: V = 150 mL
Alligation: to mix a higher strength H and a lower strength L into a target strength T, take (T − L) parts of H and (H − T) parts of L. The parts are crossed: each stock gets the distance from the target to the other stock. Water or a plain base counts as 0%. The numbers are for practice only; at the bedside always follow local protocols and have high-risk doses double-checked.
Alligation parts
50%: 30 − 10 = 20 parts
10%: 50 − 30 = 20 parts
total: 40 parts
Share the volume
V = 300·20/40 = 150 mL
Answer
V = 150 mL
Check: 150 mL of 50% + 150 mL of 10% = 300 mL.
3.Dosage calculations
Answer: V = 0.4 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.
Concentration after mixing
2000 mg/8 mL = 250 mg/mL
Volume
V = 100/250 = 0.4 mL
Answer
V = 0.4 mL
4.Dosage calculations
Answer: V = 5.6 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
5·28 = 140 mg
Volume
V = (140/125)·5 = 5.6 mL
Answer
V = 5.6 mL
5.Clinical pharmacokinetics
Answer: LD = 1050 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 = 0.7·69 = 48.3 L
Amount of active drug needed
Vd·C = 48.3·20 = 966 mg
Loading dose
LD = 966/(0.92·1) = 1050 mg
Answer
LD = 1050 mg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: τ = 14.4 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.
Creatinine clearance (Cockcroft–Gault)
CrCl = (140 − 58)·82/(72·1.4) = 66.71 mL/min
New interval
τ = 8·120/66.71 = 14.39 ≈ 14.4 h
Answer
τ = 14.4 h
In practice the interval is rounded to a convenient value such as 12, 24, 36 or 48 h.