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 0.3 mg. Draw up the volume in the 10 mL syringe: what volume V is that?
1:10 0000.3 mg
V = mL
2.Pharmacy calculationsHard
A vial holds 1000 mg of powder. You add 2.1 mL of diluent, and the powder adds 0.4 mL of volume. The prescription is 480 mg. Draw up the dose: what volume V do you give?
1000 mg2.1 mL + 0.4 mL480 mg
V = mL
3.Dosage calculationsMedium
A patient weighs 45 kg and is prescribed 15 mg/kg as a single dose. Find the dose D in mg.
45 kg15 mg/kg
D = mg
4.Dosage calculationsHard
A patient weighs 96.8 lb. The prescription is 5 mg/kg as a single dose, and the stock contains 50 mg in 1 mL. Using 1 kg = 2.2 lb, what volume V do you give?
96.8 lb5 mg/kg50 mg/1 mL1 kg = 2.2 lb
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A patient receives an IV bolus of 270 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 = 270 mgC₀ = 12 mg/Lt½ = 3 h
CL = L/h
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 57-year-old man weighs 86 kg and has a serum creatinine of 1.3 mg/dL (115 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 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/10 000 mL = 0.1 mg/mL
Volume
V = 0.3/0.1 = 3 mL
Answer
V = 3 mL
2.Pharmacy calculations
Answer: V = 1.2 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
2.1 + 0.4 = 2.5 mL
C = 1000/2.5 = 400 mg/mL
Volume
V = 480/400 = 1.2 mL
Answer
V = 1.2 mL
3.Dosage calculations
Answer: D = 675 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
15·45 = 675 mg
Answer
D = 675 mg
4.Dosage calculations
Answer: V = 4.4 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.
Weight in kg
96.8/2.2 = 44 kg
Dose
5·44 = 220 mg
Volume
V = (220/50)·1 = 4.4 mL
Answer
V = 4.4 mL
5.Clinical pharmacokinetics
Answer: CL = 5.199 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 = 270/12 = 22.5 L
Rate constant
k = 0.693/3 = 0.231 h⁻¹
Clearance
CL = 0.231·22.5 = 5.199 L/h
Answer
CL = 5.199 L/h
6.Clinical pharmacokinetics
Answer: τ = 10.5 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 − 57)·86/(72·1.3) = 76.26 mL/min
New interval
τ = 8·100/76.26 = 10.49 ≈ 10.5 h
Answer
τ = 10.5 h
In practice the interval is rounded to a convenient value such as 12, 24, 36 or 48 h.