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 contains oxacillin 2000 mg as a powder. The practice label says to add 11.5 mL of sterile water; the powder adds 1 mL to the volume. What is the concentration C in mg/mL after reconstitution?
2000 mg11.5 mL+1 mL
C = mg/mL
2.Pharmacy calculationsHard
Practice exercise (made-up values, not clinical guidance). You must prepare 200 mL of 45% ethanol from a 90% stock and purified water. How many mL V of water do you need? Round to the nearest whole mL.
90%0%45%200 mL
V = mL
3.Dosage calculationsMedium
A patient weighs 70 kg. The prescribed dose is 7.5 mg/kg per day, given in 4 equal doses. How many milligrams D are given per dose?
70 kg7.5 mg/kg/day4× per day
D = mg
4.Dosage calculationsHard
A patient weighs 81.4 lb. The prescription is 2 mg/kg as a single dose, and the stock contains 10 mg in 1 mL. Using 1 kg = 2.2 lb, what volume V do you give?
81.4 lb2 mg/kg10 mg/1 mL1 kg = 2.2 lb
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). After an IV dose of tobramycin, the level is 10 mg/L at 2 h and 3.5 mg/L at 5 h. Assume first-order elimination. Find the half-life t½.
C1 = 10 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 72-year-old man weighs 65 kg and has a serum creatinine of 2.3 mg/dL (203 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 digoxin dose is 250 mcg for a creatinine clearance of 100 mL/min, and a fraction fe = 0.7 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.
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.
Final volume
11.5 + 1 = 12.5 mL
Concentration
C = 2000/12.5 = 160 mg/mL
Answer
C = 160 mg/mL
2.Pharmacy calculations
Answer: V = 100 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
90%: 45 − 0 = 45 parts
0%: 90 − 45 = 45 parts
total: 90 parts
Water
V = 200·45/90 = 100 mL
Answer
V = 100 mL
Check: 100 mL of 90% contains 90 mL of drug, which is 45% of 200 mL. This assumes the volumes simply add up; in practice ethanol is made up to volume.
3.Dosage calculations
Answer: D = 131.3 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
7.5·70 = 525 mg
Per dose
D = 525/4 = 131.3 mg
Answer
D = 131.3 mg
4.Dosage calculations
Answer: V = 7.4 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
81.4/2.2 = 37 kg
Dose
2·37 = 74 mg
Volume
V = (74/10)·1 = 7.4 mL
Answer
V = 7.4 mL
5.Clinical pharmacokinetics
Answer: t½ = 1.981 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(10/3.5)/3 = 1.05/3 = 0.3499 h⁻¹
Half-life
t½ = 0.693/0.3499 = 1.981 h
Answer
t½ = 1.981 h
6.Clinical pharmacokinetics
Answer: D = 122 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.
Creatinine clearance (Cockcroft–Gault)
CrCl = (140 − 72)·65/(72·2.3) = 26.69 mL/min
Dose fraction (Dettli)
Q = 1 − 0.7·(1 − 26.69/100) = 0.4868
Adjusted dose
D = 0.4868·250 = 121.7 ≈ 122 mcg
Answer
D = 122 mcg
In practice the dose is rounded to a convenient amount and checked against the product information.