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 0.1 mg. Draw up the volume in the 10 mL syringe: what volume V is that?
1:10 0000.1 mg
V = mL
2.Pharmacy calculationsHard
Practice exercise (made-up values, not clinical guidance). You must prepare 500 mL of 4% chlorhexidine from a 20% stock and purified water. How many mL V of water do you need? Round to the nearest whole mL.
20%0%4%500 mL
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 weighs 184.8 lb. The prescription is 1 mg/kg as a single dose, and the stock contains 125 mg in 5 mL. Using 1 kg = 2.2 lb, what volume V do you give? Round to one decimal place.
184.8 lb1 mg/kg125 mg/5 mL1 kg = 2.2 lb
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 62 kg patient is to be loaded with digoxin tablets to reach a level of 1 mcg/L. The volume of distribution is 7 L/kg and the tablets have a bioavailability F = 0.7. Find the total oral loading dose LD in mcg.
62 kgVd = 7 L/kgC = 1 mcg/LF = 0.7
LD = mcg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 50-year-old man weighs 57 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 120 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.
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 = 0.1/0.1 = 1 mL
Answer
V = 1 mL
2.Pharmacy calculations
Answer: V = 400 mL
Alligation: to mix a higher strength H and a lower strength L into a target strength T, take (T − L) parts of H and (H − T) parts of L. The parts are crossed: each stock gets the distance from the target to the other stock. Water or a plain base counts as 0%. The numbers are for practice only; at the bedside always follow local protocols and have high-risk doses double-checked.
Alligation parts
20%: 4 − 0 = 4 parts
0%: 20 − 4 = 16 parts
total: 20 parts
Water
V = 500·16/20 = 400 mL
Answer
V = 400 mL
Check: 100 mL of 20% contains 20 g of drug, which is 4% of 500 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: V = 3.4 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
184.8/2.2 = 84 kg
Dose
1·84 = 84 mg
Volume
V = (84/125)·5 = 3.36 ≈ 3.4 mL
Answer
V = 3.4 mL
5.Clinical pharmacokinetics
Answer: LD = 620 mcg
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 = 7·62 = 434 L
Amount of active drug needed
Vd·C = 434·1 = 434 mcg
Loading dose
LD = 434/(1·0.7) = 620 mcg
Answer
LD = 620 mcg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: D = 571 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 − 50)·57/(72·1.7) = 41.91 mL/min
Dose fraction (Dettli)
Q = 1 − 0.66·(1 − 41.91/120) = 0.5705
Adjusted dose
D = 0.5705·1000 = 570.5 ≈ 571 mg
Answer
D = 571 mg
In practice the dose is rounded to a convenient amount and checked against the product information.