Dosing Patterns and Pharmacokinetics in Clinical Pharmacy

• Dosing patterns determine how a drug is administered, including the dose amount, frequency, and duration.

• Common dosing patterns include:

  • Continuous Dosing: Maintains steady plasma levels with regular dosing.

  • Intermittent Dosing: Allows drug levels to rise and fall, useful for drugs with long half-lives.

  • Loading Dose: A higher initial dose to quickly reach therapeutic levels.

  • Maintenance Dose: Keeps plasma levels within the therapeutic range.

Factors Influencing Dosing Patterns

Pharmacokinetics (PK)

• Absorption: Affected by gastrointestinal motility, pH, and food presence, impacting onset.

• Distribution: Influenced by protein binding and tissue permeability; lipophilic drugs may accumulate in fatty tissues.

• Metabolism: Primarily occurs in the liver; enzyme activity (e.g., cytochrome P450) varies, requiring dose adjustments.

• Excretion: Impacted by renal function, as impaired kidneys may lead to drug accumulation and toxicity.

Key PK Parameters Affecting Dosing:

• Bioavailability (F): Fraction of dose reaching systemic circulation; low F may need higher doses or alternative routes.

• Half-Life (t½): Time for plasma concentration to halve; longer t½ allows less frequent dosing.

• Clearance (Cl): Rate of drug elimination; low Cl requires dose reduction to avoid toxicity.

• Volume of Distribution (Vd): Indicates drug distribution extent; a large Vd suggests extensive tissue distribution.

Patient-Specific Factors

• Age, Body Weight, Organ Function, and Genetics affect drug handling and response.

Disease Characteristics

• Severity and Comorbidities: Influence PK parameters and dosing needs.

• Pathophysiological Changes: Alter absorption, distribution, or excretion.

Impact of Disease on PK and Dosing

1. Renal Impairment: Reduces excretion, requiring lower doses or longer intervals (e.g., digoxin).

2. Hepatic Dysfunction: Lowers metabolism, leading to higher drug levels; adjust dose or choose alternative drugs (e.g., warfarin).

3. Cardiovascular Disease: Affects blood flow, modifying distribution and clearance.

4. Gastrointestinal Disorders: Alter absorption; alternative routes or timing adjustments may be needed.

Individualizing Drug Therapy

1. Therapeutic Drug Monitoring (TDM): Measures plasma levels of drugs with narrow therapeutic windows for dose adjustment (e.g., aminoglycosides, anticonvulsants).

2. Adjusting Doses Based on PK and Disease:

   1. Loading Dose: Rapidly achieves therapeutic levels, based on Vd.

   2. Maintenance Dose: Maintains steady-state levels, adjusted for clearance.

   3. Dose Intervals: Extended in cases of decreased clearance.

Case Example:

• Vancomycin in Critically Ill Patients: Requires TDM due to altered Vd and clearance, balancing effective levels while avoiding toxicity.