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 0.46 mg. Draw up the volume in the 10 mL syringe: what volume V is that?
1:10 0000.46 mg
V = mL
2.Pharmacy calculationsHard
Practice exercise (made-up values, not clinical guidance). You must prepare 1500 mL of 20% dextrose by mixing 50% and 5% dextrose. How many mL V of the 50% solution do you need? Round to the nearest whole mL.
50%5%20%1500 mL
V = mL
3.Dosage calculationsMedium
A dose of 250 mg is needed from a 10% (w/v) solution. What volume V contains this dose?
250 mg10% w/v
V = mL
4.Dosage calculationsHard
A child weighing 28 kg is prescribed 5 mg/kg per dose of an oral suspension that contains 120 mg in 5 mL. What volume V do you give? Round to one decimal place.
28 kg5 mg/kg120 mg/5 mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A patient has a lidocaine clearance of 900 mL/min. What infusion rate R in mg/min keeps the steady-state level at 2.5 mg/L?
CL = 900 mL/minCss = 2.5 mg/L
R = mg/min
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 79-year-old woman weighs 72 kg and has a serum creatinine of 2.5 mg/dL (221 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 = 0.46/0.1 = 4.6 mL
Answer
V = 4.6 mL
2.Pharmacy calculations
Answer: V = 500 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
50%: 20 − 5 = 15 parts
5%: 50 − 20 = 30 parts
total: 45 parts
Share the volume
V = 1500·15/45 = 500 mL
Answer
V = 500 mL
Check: 500 mL of 50% + 1000 mL of 5% = 1500 mL.
3.Dosage calculations
Answer: V = 2.5 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
10% = 100 mg/mL
Volume
V = 250/100 = 2.5 mL
Answer
V = 2.5 mL
4.Dosage calculations
Answer: V = 5.8 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.
Dose from weight
5·28 = 140 mg
Volume
V = (140/120)·5 = 5.833 ≈ 5.8 mL
Answer
V = 5.8 mL
5.Clinical pharmacokinetics
Answer: R = 2.25 mg/min
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.
Clearance in L/min
900 mL/min = 0.9 L/min
Infusion rate
R = 0.9·2.5 = 2.25 mg/min
Answer
R = 2.25 mg/min
6.Clinical pharmacokinetics
Answer: D = 454 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 − 79)·72/(72·2.5)·0.85 = 20.74 mL/min
Dose fraction (Dettli)
Q = 1 − 0.66·(1 − 20.74/120) = 0.4541
Adjusted dose
D = 0.4541·1000 = 454.1 ≈ 454 mg
Answer
D = 454 mg
In practice the dose is rounded to a convenient amount and checked against the product information.