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 1500 mg. What volume V do you draw up? Round to one decimal place.
2000 mg19.2 mL+0.8 mL1500 mg
V = mL
2.Pharmacy calculationsHard
A vial holds 250 mg of powder. You add 2 mL of diluent, and the powder adds 0.5 mL of volume. The prescription is 200 mg. Draw up the dose: what volume V do you give?
250 mg2 mL + 0.5 mL200 mg
V = mL
3.Dosage calculationsMedium
A child weighing 14 kg is prescribed 5 mg/kg of a drug. The stock solution contains 10 mg/mL. Draw up the dose: what volume V do you give?
14 kg5 mg/kg10 mg/mL
V = mL
4.Dosage calculationsHard
The prescription is 980 micrograms. The ampoule contains 2 mg/mL. Draw up the dose in the 1 mL syringe: what volume V do you give?
980 mcg2 mg/mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). After an IV dose of gentamicin, the level is 8 mg/L at 2 h and 2 mg/L at 8 h. Assume first-order elimination. Find the elimination rate constant k.
C1 = 8 mg/L (2 h)C2 = 2 mg/L (8 h)
k = h⁻¹
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 46-year-old man weighs 77 kg and has a serum creatinine of 1.7 mg/dL (150 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 levetiracetam dose is 1000 mg for a creatinine clearance of 100 mL/min, and a fraction fe = 0.66 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.
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 = 1500/100 = 15 mL
Answer
V = 15 mL
2.Pharmacy calculations
Answer: V = 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 + 0.5 = 2.5 mL
C = 250/2.5 = 100 mg/mL
Volume
V = 200/100 = 2 mL
Answer
V = 2 mL
3.Dosage calculations
Answer: V = 7 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 = 5·14 = 70 mg
Volume
V = 70/10 = 7 mL
On the syringe
On this 10 mL syringe every small line is 0.2 mL.
Answer
V = 7 mL
4.Dosage calculations
Answer: V = 0.49 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.
Same units
2 mg/mL = 2000 mcg/mL
Volume
V = 980/2000 = 0.49 mL
Answer
V = 0.49 mL
5.Clinical pharmacokinetics
Answer: k = 0.231 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(8/2)/6 = 1.386/6 = 0.231 h⁻¹
Answer
k = 0.231 h⁻¹
6.Clinical pharmacokinetics
Answer: D = 730 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 − 46)·77/(72·1.7) = 59.13 mL/min
Dose fraction (Dettli)
Q = 1 − 0.66·(1 − 59.13/100) = 0.7303
Adjusted dose
D = 0.7303·1000 = 730.3 ≈ 730 mg
Answer
D = 730 mg
In practice the dose is rounded to a convenient amount and checked against the product information.