U01.05.006 Dosage calculations

Dosage calculations are a key component in pharmacology, ensuring appropriate therapeutic drug levels while minimizing toxicity. Here’s a structured approach to understanding loading dose, maintenance dose, and time to steady state.

Key Concepts

Loading Dose (LD)
- Used to quickly achieve a target plasma concentration.
- $\text{Loading Dose (LD)} = \frac{\text{C}_p \times \text{V}_d}{\text{F}}$
- Cp: Target plasma concentration at steady state.
- Vd: Volume of distribution.
- F: Bioavailability (fraction of the drug that reaches systemic circulation).
Maintenance Dose (MD)
- Maintains the desired drug concentration in the plasma over time.
- $\text{Maintenance Dose (MD)} = \frac{\text{Cp} \times \text{CL} \times \tau}{\text{F}}$
- C_p: Target plasma concentration at steady state.
- C_L: Clearance of the drug.
- τ: Dosage interval (time between doses).
- F: Bioavailability.
Time to Steady State (TSS)
- Primarily determined by the drug’s half-life (t_1/2).
- Key Point: Time to steady state is independent of dose or dosing frequency.
Renal or Liver Disease Adjustments
- Maintenance Dose: Typically decreased due to impaired drug clearance.
- Loading Dose: Usually remains unchanged because it is based on V_d

Summary Table

\text{Loading Dose (LD)} = \frac{\text{C}_p \times \text{V}_d}{\text{F}}

\text{Maintenance Dose (MD)} = \frac{\text{Cp} \times \text{CL} \times \tau}{\text{F}}

Term	Formula	Key Parameters
Loading Dose (LD)	$\text{Loading Dose (LD)} = \frac{\text{C}_p \times \text{V}_d}{\text{F}}$	Plasma concentration, volume of distribution, bioavailability.
Maintenance Dose (MD)	$\text{Maintenance Dose (MD)} = \frac{\text{Cp} \times \text{CL} \times \tau}{\text{F}}$	Plasma concentration, clearance, dosing interval, bioavailability.
Time to Steady State	~4-5 half-lives (t_1/2)	Depends on half-life, independent of dose or frequency.

Points to Remember

Loading Dose: Quickly achieves the desired plasma concentration.
Maintenance Dose: Keeps plasma levels consistent over time.
Steady State: Takes approximately 4-5 half-lives, irrespective of dosing strategy.
Disease Adjustments: Adjust maintenance dose for renal or hepatic impairment but not loading dose.

Tips for USMLE Step 1 Preparation

Understand the formulae: Memorize and practice applying the LD and MD equations in different clinical scenarios.
Focus on concepts: Recognize when to adjust dosing based on patient conditions like organ dysfunction.
Practice Questions: Solve practice problems to reinforce your understanding of steady-state and half-life dynamics.

References

Katzung, B. G., & Trevor, A. J. Basic & Clinical Pharmacology.
Brunton, L. L., & Hilal-Dandan, R. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics.

USMLE Step 1 Review Series

Curriculum