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 1:1000. You need 0.31 mg. Draw up the volume in the 1 mL syringe: what volume V is that?
1:10000.31 mg
V = mL
2.Pharmacy calculationsHard
A vial holds 500 mg of powder. You add 1.7 mL of diluent, and the powder adds 0.8 mL of volume. The prescription is 420 mg. Draw up the dose: what volume V do you give?
500 mg1.7 mL + 0.8 mL420 mg
V = mL
3.Dosage calculationsMedium
A patient weighs 30 kg. The prescribed dose is 7.5 mg/kg per day, given in 4 equal doses. How many milligrams D are given per dose?
30 kg7.5 mg/kg/day4× per day
D = mg
4.Dosage calculationsHard
A patient weighs 83.6 lb. The prescription is 1 mg/kg as a single dose, and the stock contains 40 mg in 1 mL. Using 1 kg = 2.2 lb, what volume V do you give?
83.6 lb1 mg/kg40 mg/1 mL1 kg = 2.2 lb
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 70 kg patient is to be loaded intravenously with aminophylline to reach a theophylline level of 12 mg/L. The volume of distribution is 0.5 L/kg and the salt factor is S = 0.8. Find the loading dose LD of aminophylline in mg.
70 kgVd = 0.5 L/kgC = 12 mg/LS = 0.8
LD = mg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A theophylline infusion is started without a loading dose. The half-life in this patient is 9 h. How long t does it take to reach 90% of the steady-state level?
t½ = 9 h90% Css
t = h
3Solutions
1.Pharmacy calculations
Answer: V = 0.31 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.
Strength in mg/mL
1000 mg/1000 mL = 1 mg/mL
Volume
V = 0.31/1 = 0.31 mL
Answer
V = 0.31 mL
2.Pharmacy calculations
Answer: V = 2.1 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
1.7 + 0.8 = 2.5 mL
C = 500/2.5 = 200 mg/mL
Volume
V = 420/200 = 2.1 mL
Answer
V = 2.1 mL
3.Dosage calculations
Answer: D = 56.25 mg
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.
Total per day
7.5·30 = 225 mg
Per dose
D = 225/4 = 56.25 mg
Answer
D = 56.25 mg
4.Dosage calculations
Answer: V = 0.95 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
83.6/2.2 = 38 kg
Dose
1·38 = 38 mg
Volume
V = (38/40)·1 = 0.95 mL
Answer
V = 0.95 mL
5.Clinical pharmacokinetics
Answer: LD = 525 mg
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 = 0.5·70 = 35 L
Amount of active drug needed
Vd·C = 35·12 = 420 mg
Loading dose
LD = 420/(0.8·1) = 525 mg
Answer
LD = 525 mg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: t = 29.9 h
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.