m1l1 // measurements of drug con to pharmaco models - PART 2

Biologic samples

Biologic samples

obtain data regarding drug concentrations

INVASIVE METHOD

• Blood

  • Whole Blood

    • Serum & Plasma

• Spinal fluid

• Synovial fluid

• Tissue biopsy

NONINVASIVE METHOD

• Urine

• Saliva

• Feces

• Expired air

Whole blood 2

obtained by Venous puncture and contains an anticoagulant such as heparin or EDTA 2

Whole blood 1

contains all the cellular and protein elements of blood 1

Serum

obtained from Whole blood after the blood is allowed to clot and the clot is removed

Serum

does not contain the cellular elements, fibrinogen, or the other clotting factors from the blood

Plasma

The liquid supernatant obtained after centrifugation of non-clotted whole blood that contains an anticoagulant (heparin)

Plasma

is the noncellular fraction of whole blood and contains all the proteins including albumin

Plasma

perfuses all the tissues of the body, including the cellular elements in the blood

tissue drug concentrations

Changes in the drug concentration in plasma will reflect changes in _

Drug concentration in tissues

Used to ascertain if the drug reached the tissues and reached the proper concentration within the tissue.

Disadvantages of Drug concentration in tissues

• Drug concentration measurement difficult (because only a small sample of tissue is removed)

• Drug concentrations in tissue biopsies may not reflect drug concentration in other tissues nor the drug concentration in all parts of the tissue from which the biopsy material was removed

Urine

an indirect method to ascertain the bioavailability of a drug // only applicable to first order elimination process

Urine

the rate and extent of drug excreted in the urine reflects the rate and extent of systemic drug absorption

Feces

May reflect drug that has not been absorbed after an oral dose

Feces

May reflect drug that has been expelled by biliary secretion after systemic absorption

Fecal collection

is performed to recover certain solid oral dosage forms that do not dissolve in the gastrointestinal tract but slowly leach out drug

Saliva

drug levels tend to approximate free drug

free drug

only diffuses in the saliva // unbound to plasma proteins

Saliva/plasma drug concentration

is mostly influenced by the pKa of the drug and the pH of the saliva

secondary indicator

Use of salivary drug concentrations as a therapeutic indicator should be used with caution and preferably as a _

drugs bound to albumin

remain in the systemic circulation

The Plasma Level – Time Curve

Generated by obtaining the drug concentration in plasma samples taken at various time intervals after a drug product is administered

plasma drug concentration

most common and most useful clinically

Minimum effective concentration

reflects the minimum concentration of drug needed at the receptors to produce the desired pharmacologic effect

Minimum toxic concentration

represents the drug concentration needed to just barely produce a toxic effect

Duration of action

the difference between the onset time and the time for the drug to decline back to the MEC

Intensity of pharmacologic effect

proportional to the number of drug receptors occupied, which is reflected in the observation that higher plasma drug concentrations produce a greater pharmacologic response, up to a maximum

Onset time

time required for the drug to reach the MEC

Peak plasma level

• A.k.a. maximum drug concentration (Cmax)

• related to the dose, the rate constant for absorption, and the elimination constant of the drug

Time for peak plasma level

• time of maximum drug concentration in the plasma (Tmax)

• a rough marker of average rate of drug absorption

Area under the curve (AUC)

related to the amount of drug absorbed systemically

• extent of drug absorption

• most important parameter

tmax

rate of drug absorption

cmax

rate and extent of drug absorption

Intensity of the pharmacologic or toxic effect of a drug

is often related to the concentration of the drug at the receptor site, usually located in the tissue cells

most of the tissue cells

are richly perfused with tissue fluids or plasma

responsive method

measuring the plasma drug level is a _ of monitoring the course of therapy

Clinically, individual variations in the pharmacokinetics of drugs are quite common

• Monitoring the concentration of drugs ascertains that the calculated dose actually delivers the plasma level required for therapeutic effect

With some drugs, receptor expression and/or sensitivity in individuals varies

• Monitoring of plasma levels is needed to distinguish the patient who is receiving too much of a drug from the patient who is supersensitive to the drug

A patient's physiologic functions

may be affected by disease, nutrition, environment, concurrent drug therapy, and other factors

Monitoring plasma drug concentrations Clinical uses:

1. Allows for the adjustment of the drug dosage in order to individualize and optimize therapeutic drug regimens

2. May provide a guide to the progress of the disease state and enable the investigator to modify the drug dosage accordingly in the presence of alteration in physiologic functions due to disease

DRAWBACKS

• Plasma drug levels are relatively useless for dosage adjustment in the absence of pharmacokinetic information

• NEEDED PK INFO:

  • TIME when the blood sample was drawn

  • DOSE of the drug that was given

  • ROUTE OF ADMINISTRATION

Drug therapy regimen

• Estimation of drug dosing

• Prediction of the time course of drug efficacy for a given dose

dynamic state

Drugs are in _ within the body

As DRUGS move between TISSUES and FLUIDS

• Binds with PLASMA or CELLULAR COMPONENTS

• Metabolized

simultaneously

• Drug events often happen _