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 0.62 mg. Draw up the volume in the 10 mL syringe: what volume V is that?
1:10 0000.62 mg
V = mL
2.Pharmacy calculationsHard
A vial holds 250 mg of powder. You add 3.8 mL of diluent, and the powder adds 0.2 mL of volume. The prescription is 187.5 mg. Draw up the dose: what volume V do you give?
250 mg3.8 mL + 0.2 mL187.5 mg
V = mL
3.Dosage calculationsMedium
A child weighing 40 kg is prescribed 4 mg/kg of a drug. The stock solution contains 40 mg/mL. Draw up the dose: what volume V do you give?
40 kg4 mg/kg40 mg/mL
V = mL
4.Dosage calculationsHard
You must prepare 500 mL of a 1% (w/v) solution from a 50% (w/v) stock solution. What volume of stock V₁ do you need?
C₁ = 50%C₂ = 1%V₂ = 500 mL
V₁ = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). After an IV dose of vancomycin, the level is 25 mg/L at 1 h and 12.5 mg/L at 13 h. Assume first-order elimination. Find the elimination rate constant k.
C1 = 25 mg/L (1 h)C2 = 12.5 mg/L (13 h)
k = h⁻¹
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 49-year-old woman weighs 85 kg and has a serum creatinine of 3 mg/dL (265 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 ciprofloxacin dose is 500 mg for a creatinine clearance of 100 mL/min, and a fraction fe = 0.6 of the drug is excreted unchanged by the kidneys. Using the Dettli dose fraction Q = 1 − fe·(1 − CrCl/normal CrCl), find the adjusted dose D. Round to the nearest whole number.
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 = 0.62/0.1 = 6.2 mL
Answer
V = 6.2 mL
2.Pharmacy calculations
Answer: V = 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
3.8 + 0.2 = 4 mL
C = 250/4 = 62.5 mg/mL
Volume
V = 187.5/62.5 = 3 mL
Answer
V = 3 mL
3.Dosage calculations
Answer: V = 4 mL
Drawing up a dose: volume = (prescribed dose/stock strength) × stock volume. Convert to the same units first, then check that the volume fits the syringe and lands on one of its graduations.
Dose from body weight
D = 4·40 = 160 mg
Volume
V = 160/40 = 4 mL
On the syringe
On this 10 mL syringe every small line is 0.2 mL.
Answer
V = 4 mL
4.Dosage calculations
Answer: V₁ = 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.
Volume of stock
V₁ = 1·500/50 = 10 mL
Answer
V₁ = 10 mL
5.Clinical pharmacokinetics
Answer: k = 0.05776 h⁻¹
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.
Elimination rate constant
k = ln(25/12.5)/12 = 0.6931/12 = 0.05776 h⁻¹
Answer
k = 0.05776 h⁻¹
6.Clinical pharmacokinetics
Answer: D = 291 mg
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 − 49)·85/(72·3)·0.85 = 30.44 mL/min
Dose fraction (Dettli)
Q = 1 − 0.6·(1 − 30.44/100) = 0.5826
Adjusted dose
D = 0.5826·500 = 291.3 ≈ 291 mg
Answer
D = 291 mg
In practice the dose is rounded to a convenient amount and checked against the product information.