Application of Pharmacokinetics

It is for clinical situation.

1. Application of Pharmacokinetics in Clinical S ituation

2. Presented by : Md. Abdullah Al-Fahim B.PHRM, East West University, Dhaka, Bangladesh.

3. Pharmacokinetics: Pharmacokinetics is currently defined as the study of the time course of drug absorption, distribution, metabolism, and excretion. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Primary goals: Enhancing efficacy Decreasing toxicity ( Shargel & Yu’s,2016).

4. Application of Pharmacokinetic to Clinical Situations: Select drug. Design dosage regimen. Evaluate patient response. Determine need for measuring serum drug concentrations. Assay for drug concentration in biological fluids. Perform pharmacokinetic evaluation of drug concentrations. Readjust dosage regimen, if necessary. Monitor serum drug concentrations. Recommend special requirements. ( Shargel & Yu’s,2016).

5. Select drug:

6. Design dosage regimen:

7. Evaluation of Patient’s Response: the practitioner should evaluate the patient’s clinical response. dosage regimen should be reviewed for adequacy, accuracy, and patient compliance with the drug therapy. sound clinical judgment may preclude the need for measuring serum drug concentrations.

8. Measurement of Drug Concentrations Drug concentrations are measured for - Clinical drug monitoring to improve drug therapy Drug abuse screening Toxicology evaluation such as poisoning and drug overdose. Measurement of the presence of abused drugs ( Shargel & Yu’s,2016).

9. Assay for Drug Drug analyses are usually performed either by a clinical chemistry laboratory or by a clinical pharmacokinetics laboratory by- High-pressure liquid chromatography coupled with mass spectrometry (LCMS) Immunoassay ( Shargel & Yu’s,2016).

10. Assay for Drug The methods used by the analytic laboratory may depend on such factors as the - Physicochemical characteristics of the drug Target drug concentration Amount (volume) Nature of the biologic specimen (serum, urine, saliva) Available instrumentation Cost for each assay Analytical skills of the laboratory personnel ( Shargel & Yu’s,2016).

11. Assay for Drug Methods used for the assay of drugs in serum or plasma should be validated by- Specificity Linearity Sensitivity Precision Accuracy Stability and Ruggedness ( Shargel & Yu’s,2016).

12. Pharmacokinetic Evaluation The assay results may show that the patient’s serum drug levels are higher, lower, or similar to the expected serum levels. The pharmacist should evaluate these results while considering the patient and the patient’s pathophysiologic condition Therefore, the clinician or pharmacist should evaluate the data using sound clinical judgment and observation. The therapeutic decision should not be based solely on serum drug concentrations ( Shargel & Yu’s,2016).

13. READJUSTMENT DOSAGE REGIMEN Factors of selecting drug The body weight of the patient The patient’s renal function The patient’s age Concomitant disease states ( Shargel & Yu’s,2016).

14. DESIGN OF DOSAGE REGIMENS Dosage Regimens Based on Population Averages Individualized Dosage Regimens Dosage Regimens Based on Partial Pharmacokinetic Parameters Nomograms and Tabulations in Dosage Regimen Designs Monitoring Serum Drug Concentrations ( Shargel & Yu’s,2016).

15. DOSAGE REGIMENS BASED ON POPULATION AVERAGES pharmacokinetic parameters such as Absorption rate constant ( ka ) Bioavailability factor F Apparent volume of distribution VD Elimination rate constant k are assumed to remain constant. This is One-compartment model . ( Shargel & Yu’s,2016).

16. MONITORING SERUM DRUG CONCENTRATIONS In many cases, the patient’s pathophysiology may be unstable, either improving or deteriorating further. For example, proper therapy for congestive heart failure will improve cardiac output and renal perfusion, response can be monitored in lieu of actual serum drug concentration, thereby increasing renal drug clearance. prothrombin time might be useful for monitoring anticoagulant therapy blood pressure monitoring for antihypertensive agents. ( Shargel & Yu’s,2016).

17. Serum Concentrations Lower Than Anticipated Patient compliance Wrong drug product (controlled release instead of immediate release) Poor bioavailability Rapid elimination (efficient metabolizer) Reduced plasma–protein binding Serum Concentrations Higher Than Anticipated Patient compliance Wrong drug product (immediate release instead of controlled release) Rapid bioavailability Smaller-than-anticipated apparent volume of distribution Slow elimination (poor metabolizer) Increased plasma–protein binding

18. SPECIAL RECOMMENDATIONS The patient may be taking the drug after a meal instead of before or may not be adhering to a special diet ( eg , low-salt diet). Therefore, the patient may need special instructions that are simple and easy to follow . to discontinue the drug prescribe another drug from the same therapeutic class . ( Shargel & Yu’s,2016).

19. Reference Shargel and Yu’s(2016) Applied Biopharmaceutics & Pharmacokinetics. Seventh Edition. New York : McGraw-Hill Education.