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 of penicillin G contains 5 000 000 units. Its practice label gives three strengths (see the table). You add 18.2 mL of diluent. The prescribed dose is 2 000 000 units. What volume V do you draw up? Round to one decimal place.
18.2 mL → 250 000 units/mL2 000 000 units
V = mL
2.Pharmacy calculationsHard
A vial holds 2000 mg of powder. You add 1.8 mL of diluent, and the powder adds 0.2 mL of volume. The prescription is 1300 mg. Draw up the dose: what volume V do you give?
2000 mg1.8 mL + 0.2 mL1300 mg
V = mL
3.Dosage calculationsMedium
A patient weighs 90 kg and is prescribed 2 mg/kg as a single dose. Find the dose D in mg.
90 kg2 mg/kg
D = mg
4.Dosage calculationsHard
An infusion contains 40000 units of a drug in 250 mL. The prescription is 1200 units per hour. At what rate R do you set the pump, in mL/h?
40000 units/250 mL1200 units/h
R = mL/h
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A patient receives an IV bolus of 180 mg of tobramycin. The level back-extrapolated to time zero is 12 mg/L and the half-life is 3 h. Find the clearance CL in L/h.
D = 180 mgC₀ = 12 mg/Lt½ = 3 h
CL = L/h
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 48-year-old man weighs 73 kg and has a serum creatinine of 3.6 mg/dL (318 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.
Concentration from the label
18.2 mL → 250 000 units/mL
Volume to give
V = 2 000 000/250 000 = 8 mL
Answer
V = 8 mL
2.Pharmacy calculations
Answer: V = 1.3 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
1.8 + 0.2 = 2 mL
C = 2000/2 = 1000 mg/mL
Volume
V = 1300/1000 = 1.3 mL
Answer
V = 1.3 mL
3.Dosage calculations
Answer: D = 180 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.
Dose
2·90 = 180 mg
Answer
D = 180 mg
4.Dosage calculations
Answer: R = 7.5 mL/h
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
40000/250 = 160 units/mL
Pump rate
R = 1200/160 = 7.5 mL/h
Answer
R = 7.5 mL/h
5.Clinical pharmacokinetics
Answer: CL = 3.466 L/h
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 = 180/12 = 15 L
Rate constant
k = 0.693/3 = 0.231 h⁻¹
Clearance
CL = 0.231·15 = 3.466 L/h
Answer
CL = 3.466 L/h
6.Clinical pharmacokinetics
Answer: τ = 37.1 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 − 48)·73/(72·3.6) = 25.91 mL/min
New interval
τ = 8·120/25.91 = 37.05 ≈ 37.1 h
Answer
τ = 37.1 h
In practice the interval is rounded to a convenient value such as 12, 24, 36 or 48 h.