Clinical Pharmacokinetics: Summary

WHAT IF?

Q1. (per Dr. Swecker) If I double the dose of an antibiotic given to cattle, what SHOULD happen to the withdrawal time?

Q2. Alteration of what pharmacokinetic constants might make my answer to Q1 WRONG? (what MIGHT BE wrong with the simple/obvious answer)

Pharmacokinetic Summary

Dose-Interval, F, and Clt control the average concentration.

Dose, ka, lz and ACCUMULATION control the peak.

Interval, lz and ACCUMULATION control the trough.

View a practice Excel Worksheet at http://cpharm.vetmed.vt.edu/vm8784/KINETICS/summary.xls

Constant Abbreviation Clinical effects
Absorption rate constant ka Diarrhea (oral), Constipation(oral), Inflammation (oral, subQ, IM), Infiltration of bowel wall (oral), Hypermotility, Hypomotility, Dehydration (subQ), Shock (oral, subQ, IM), Ambient temperature (subQ)
Fraction Absorbed F Diarrhea (oral), Constipation(oral), Inflammation (oral, subQ, IM), Infiltration of bowel wall (oral), Hypermotility, Hypomotility, Dehydration (subQ), Shock (oral, subQ, IM), Ambient temperature (subQ)
Clearance Clt (Cl, Clr, Clh) Organ failure, Cardiovascular disease, etc.
Volume of Distribution V (Vz, Vd) Dehydration, Overhydration, Heart failure, etc.
Half-Life T1/2 Produced by interaction of Volume and Clearance
Elimination rate constant λz (k, kel) Reciprocal of T1/2

Topic Summary: Pharmacokinetics

  1. Pharmacokinetics and therapeutic concentration monitoring AUGMENT but never REPLACE critical evaluation of the patient's response to the drug.


  2. Pharmacokinetics describes the relationship between drug doses and the concentration of the drug in the body.

  3. Clearance is set by the animal (species, state of health) and the chemistry of the drug and is a direct reflection of the ability of the organs of elimination to remove drug from the fluid (body water) in which it is dissolved. In patients, clearance values most accurately reflect the function of the organs of elimination. Clearance is used to calculate the average concentration produced in a patient for a given rate of drug administration.

  4. Half-life and elimination rate are reciprocal terms used to calculate the (fractional) disappearance of a drug from the body. Half-life values in patients may be altered because clearance changes (diseased organs of elimination) or because the volume of distribution changes (changes in body water, vascular permeability). Half-life indicates the time required to remove fixed portions (i.e. 97%) of the drug from the body and the time required to reach a steady state (5 x T1/2 = 97% of steady state).

  5. Volumes of distribution are used to calculate the concentrations of drug (in various compartments) from known amounts. Volume of distribution changes in patients are related to body water composition, vascular permeability, protein binding, etc. A change in volume of distribution that does not cause a change in clearance (organ function) must cause a change in half-life and elimination rate constant.

  6. Therapeutic monitoring of aminoglycoside antibiotics is done to improve efficacy and reduce toxicity. This is accomplished by matching patient pharmacokinetics to specific target peak and trough concentrations.

  7. Therapeutic monitoring of digoxin is done for the purposes of:

    confirming toxicity
    dose adjustment
    recommendations following intoxication.

  8. Therapeutic monitoring of anticonvulsants is done for the purposes of:

    assessing efficacy
    dose adjustment recommendations following intoxication.