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.PharmacologyMedium
How are most medication doses for children calculated?
ABy the child's age in years only
BBy the child's height alone
CBy giving half of the adult dose to all children under 12
DBy body weight in kilograms, or sometimes body surface area
2.PharmacologyHard
A patient on long-term lithium passes large amounts of dilute urine and is always thirsty. What is the most likely explanation?
ALithium causes type 1 diabetes by destroying the pancreatic beta cells
BThe patient is drinking too much and lithium is unrelated
CLithium increases ADH release from the pituitary
DLithium blocks the kidney's response to ADH (nephrogenic diabetes insipidus)
3.Dosage calculationsMedium
A vial contains 2 g of powder. The label says: add 7.4 mL of water for injection to give a total volume of 8 mL. The prescription is 100 mg. What volume V of the reconstituted solution do you give?
2 g+ 7.4 mL → 8 mL100 mg
V = mL
4.Dosage calculationsHard
The prescription is 930 micrograms. The ampoule contains 1 mg/mL. Draw up the dose in the 1 mL syringe: what volume V do you give?
930 mcg1 mg/mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A patient receives an IV bolus of 200 mg of tobramycin. The level back-extrapolated to time zero is 8 mg/L and the half-life is 2.5 h. Find the clearance CL in L/h.
D = 200 mgC₀ = 8 mg/Lt½ = 2.5 h
CL = L/h
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 58-year-old man weighs 78 kg and has a serum creatinine of 2.4 mg/dL (212 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 gentamicin regimen is 80 mg every 8 h for a creatinine clearance of 120 mL/min. Keeping the dose, the interval is lengthened in proportion to the fall in clearance. Find the new dosing interval τ. Round to one decimal place.
Answer: D · By body weight in kilograms, or sometimes body surface area
Why this is the answer
Children's doses are usually weight-based, sometimes using body surface area, and must not exceed the adult maximum. Accurate, recent weight in kilograms is essential.
Answer
D · By body weight in kilograms, or sometimes body surface area
2.Pharmacology
Answer: D · Lithium blocks the kidney's response to ADH (nephrogenic diabetes insipidus)
Why this is the answer
Lithium interferes with ADH action in the collecting duct, causing polyuria and polydipsia. Dehydration from this can raise lithium levels further, so fluid balance matters.
Answer
D · Lithium blocks the kidney's response to ADH (nephrogenic diabetes insipidus)
3.Dosage calculations
Answer: V = 0.4 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.
Concentration after mixing
2000 mg/8 mL = 250 mg/mL
Volume
V = 100/250 = 0.4 mL
Answer
V = 0.4 mL
4.Dosage calculations
Answer: V = 0.93 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.
Same units
1 mg/mL = 1000 mcg/mL
Volume
V = 930/1000 = 0.93 mL
Answer
V = 0.93 mL
5.Clinical pharmacokinetics
Answer: CL = 6.931 L/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.
Volume of distribution
Vd = 200/8 = 25 L
Rate constant
k = 0.693/2.5 = 0.2773 h⁻¹
Clearance
CL = 0.2773·25 = 6.931 L/h
Answer
CL = 6.931 L/h
6.Clinical pharmacokinetics
Answer: τ = 25.9 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.
Creatinine clearance (Cockcroft–Gault)
CrCl = (140 − 58)·78/(72·2.4) = 37.01 mL/min
New interval
τ = 8·120/37.01 = 25.94 ≈ 25.9 h
Answer
τ = 25.9 h
In practice the interval is rounded to a convenient value such as 12, 24, 36 or 48 h.