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 1:1000. You need 0.1 mg. Draw up the volume in the 1 mL syringe: what volume V is that?
1:10000.1 mg
V = mL
2.Pharmacy calculationsHard
Practice exercise (made-up values, not clinical guidance). You must prepare 750 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%750 mL
V = mL
3.Dosage calculationsMedium
A patient weighs 60 kg. The prescribed dose is 20 mg/kg per day, given in 3 equal doses. How many milligrams D are given per dose?
60 kg20 mg/kg/day3× per day
D = mg
4.Dosage calculationsHard
A child weighing 16 kg is prescribed 15 mg/kg per dose of an oral suspension that contains 40 mg in 1 mL. What volume V do you give?
16 kg15 mg/kg40 mg/1 mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 73 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.
73 kgVd = 0.7 L/kgC = 15 mg/LS = 0.92
LD = mg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). An 84-year-old man weighs 76 kg and has a serum creatinine of 1.5 mg/dL (133 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 vancomycin regimen is 1000 mg every 12 h for a creatinine clearance of 100 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.
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/1000 mL = 1 mg/mL
Volume
V = 0.1/1 = 0.1 mL
Answer
V = 0.1 mL
2.Pharmacy calculations
Answer: V = 375 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 = 750·20/40 = 375 mL
Answer
V = 375 mL
Check: 375 mL of 50% + 375 mL of 10% = 750 mL.
3.Dosage calculations
Answer: D = 400 mg
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.
Total per day
20·60 = 1200 mg
Per dose
D = 1200/3 = 400 mg
Answer
D = 400 mg
4.Dosage calculations
Answer: V = 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
15·16 = 240 mg
Volume
V = (240/40)·1 = 6 mL
Answer
V = 6 mL
5.Clinical pharmacokinetics
Answer: LD = 833.2 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 = 0.7·73 = 51.1 L
Amount of active drug needed
Vd·C = 51.1·15 = 766.5 mg
Loading dose
LD = 766.5/(0.92·1) = 833.2 mg
Answer
LD = 833.2 mg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: τ = 30.5 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 − 84)·76/(72·1.5) = 39.41 mL/min
New interval
τ = 12·100/39.41 = 30.45 ≈ 30.5 h
Answer
τ = 30.5 h
In practice the interval is rounded to a convenient value such as 12, 24, 36 or 48 h.