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 2000 mg as a powder. The practice label says to add 19.2 mL of sterile water; the powder adds 0.8 mL to the volume. The prescribed dose is 1000 mg. What volume V do you draw up? Round to one decimal place.
2000 mg19.2 mL+0.8 mL1000 mg
V = mL
2.Pharmacy calculationsHard
A vial holds 500 mg of powder. You add 4.4 mL of diluent, and the powder adds 0.6 mL of volume. The prescription is 450 mg. Draw up the dose: what volume V do you give?
500 mg4.4 mL + 0.6 mL450 mg
V = mL
3.Dosage calculationsMedium
A prefilled syringe of epinephrine (adrenaline) is labelled 1:10 000 (0.1 mg/mL). The prescription is 1 mg IV in cardiac arrest. What volume V do you give?
1:10 0001 mg
V = mL
4.Dosage calculationsHard
A child weighing 28 kg is prescribed 12.5 mg/kg per dose of an oral suspension that contains 200 mg in 5 mL. What volume V do you give? Round to one decimal place.
28 kg12.5 mg/kg200 mg/5 mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 68 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.
68 kgVd = 0.7 L/kgC = 15 mg/LS = 0.92
LD = mg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 46-year-old man weighs 88 kg and has a serum creatinine of 2.6 mg/dL (230 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 gentamicin regimen is 80 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
19.2 + 0.8 = 20 mL
Concentration
2000/20 = 100 mg/mL
Volume to give
V = 1000/100 = 10 mL
Answer
V = 10 mL
2.Pharmacy calculations
Answer: V = 4.5 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
4.4 + 0.6 = 5 mL
C = 500/5 = 100 mg/mL
Volume
V = 450/100 = 4.5 mL
Answer
V = 4.5 mL
3.Dosage calculations
Answer: V = 10 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.
Concentration
1:10 000 = 1 g/10000 mL = 0.1 mg/mL
Volume
V = 1/0.1 = 10 mL
Answer
V = 10 mL
US labels now state mg/mL (1 mg/mL = 1:1000; 0.1 mg/mL = 1:10 000). Never give 1 mg/mL epinephrine IV push.
4.Dosage calculations
Answer: V = 8.8 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
12.5·28 = 350 mg
Volume
V = (350/200)·5 = 8.75 ≈ 8.8 mL
Answer
V = 8.8 mL
5.Clinical pharmacokinetics
Answer: LD = 776.1 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 = 0.7·68 = 47.6 L
Amount of active drug needed
Vd·C = 47.6·15 = 714 mg
Loading dose
LD = 714/(0.92·1) = 776.1 mg
Answer
LD = 776.1 mg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: τ = 21.7 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 − 46)·88/(72·2.6) = 44.19 mL/min
New interval
τ = 8·120/44.19 = 21.73 ≈ 21.7 h
Answer
τ = 21.7 h
In practice the interval is rounded to a convenient value such as 12, 24, 36 or 48 h.