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 0.32 mg. Draw up the volume in the 10 mL syringe: what volume V is that?
1:10 0000.32 mg
V = mL
2.Pharmacy calculationsHard
Practice exercise (made-up values, not clinical guidance). You must prepare 200 mL of 5% 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%5%200 mL
V = mL
3.Dosage calculationsMedium
An ampoule of epinephrine (adrenaline) is labelled 1:1000 (1 mg/mL). The prescription is 0.3 mg IM for anaphylaxis. What volume V do you draw up?
1:10000.3 mg
V = mL
4.Dosage calculationsHard
The prescription is 3250 units of a drug that comes as 5000 units/mL. Draw up the dose in the 1 mL syringe: what volume V do you give?
3250 units5000 units/mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 59 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.
59 kgVd = 7 L/kgC = 1 mcg/LF = 0.7
LD = mcg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A vancomycin infusion is started without a loading dose. The half-life in this patient is 10 h. How long t does it take to reach 50% of the steady-state level?
t½ = 10 h50% Css
t = h
3Solutions
1.Pharmacy calculations
Answer: V = 3.2 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.
Strength in mg/mL
1000 mg/10 000 mL = 0.1 mg/mL
Volume
V = 0.32/0.1 = 3.2 mL
Answer
V = 3.2 mL
2.Pharmacy calculations
Answer: V = 150 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%: 5 − 0 = 5 parts
0%: 20 − 5 = 15 parts
total: 20 parts
Water
V = 200·15/20 = 150 mL
Answer
V = 150 mL
Check: 50 mL of 20% contains 10 g of drug, which is 5% of 200 mL.
3.Dosage calculations
Answer: V = 0.3 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 = 0.3/1 = 0.3 mL
Answer
V = 0.3 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 = 0.65 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.
Volume
V = 3250/5000 = 0.65 mL
On the syringe
On this 1 mL syringe every small line is 0.01 mL.
Answer
V = 0.65 mL
5.Clinical pharmacokinetics
Answer: LD = 590 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 = 7·59 = 413 L
Amount of active drug needed
Vd·C = 413·1 = 413 mcg
Loading dose
LD = 413/(1·0.7) = 590 mcg
Answer
LD = 590 mcg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: t = 10 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.