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 3.2 mL of diluent. The prescribed dose is 1 500 000 units. What volume V do you draw up? Round to one decimal place.
3.2 mL → 1 000 000 units/mL1 500 000 units
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 112.5 mg. Draw up the dose: what volume V do you give?
250 mg3.8 mL + 0.2 mL112.5 mg
V = mL
3.Dosage calculationsMedium
An ampoule of epinephrine (adrenaline) is labelled 1:1000 (1 mg/mL). The prescription is 0.5 mg IM for anaphylaxis. What volume V do you draw up?
1:10000.5 mg
V = mL
4.Dosage calculationsHard
A patient is 113 cm tall and weighs 30 kg. The prescription is 100 mg/m². Using the Mosteller formula BSA = √(height (cm) × weight (kg)/3600), find the dose D in mg.
113 cm30 kg100 mg/m²
D = mg
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 3.5 mg/L at 5 h. Assume first-order elimination. Find the half-life t½.
C1 = 8 mg/L (2 h)C2 = 3.5 mg/L (5 h)
t½ = h
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 74 kg patient has a digoxin level of 0.2 mcg/L; the target is 0.8 mcg/L. The volume of distribution is 7 L/kg and the tablets have F = 0.7. What extra loading dose LD raises the level to the target?
74 kgVd = 7 L/kgC = 0.2 → 0.8 mcg/LF = 0.7
LD = mcg
3Solutions
1.Pharmacy calculations
Answer: V = 1.5 mL
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
3.2 mL → 1 000 000 units/mL
Volume to give
V = 1 500 000/1 000 000 = 1.5 mL
Answer
V = 1.5 mL
2.Pharmacy calculations
Answer: V = 1.8 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 = 112.5/62.5 = 1.8 mL
Answer
V = 1.8 mL
3.Dosage calculations
Answer: V = 0.5 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
1:1000 = 1 g/1000 mL = 1 mg/mL
Volume
V = 0.5/1 = 0.5 mL
Answer
V = 0.5 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: D = 97.04 mg
Body-surface-area dosing: many cytotoxic and some paediatric doses are prescribed per square metre of body surface area: dose (mg) = dose per m² × BSA (m²). The Mosteller formula estimates BSA = √(height (cm) × weight (kg)/3600).
Body surface area
BSA = √(113·30/3600) = √0.9417 = 0.9704 m²
Dose
D = 100·0.9704 = 97.04 mg
Answer
D = 97.04 mg
5.Clinical pharmacokinetics
Answer: t½ = 2.515 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.
Elimination rate constant
k = ln(8/3.5)/3 = 0.8267/3 = 0.2756 h⁻¹
Half-life
t½ = 0.693/0.2756 = 2.515 h
Answer
t½ = 2.515 h
6.Clinical pharmacokinetics
Answer: LD = 444 mcg
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.
Volume of distribution
Vd = 7·74 = 518 L
Rise needed
0.8 − 0.2 = 0.6 mcg/L
Loading dose
LD = 518·0.6/(1·0.7) = 444 mcg
Answer
LD = 444 mcg
In practice the dose is rounded to a convenient amount.