pharmacy, we need to see how clinical pharmacokinetics fits into the pharmaceutical care process.

Transcription

1 Therapeutic drug monitoring (TDM) Is a tool that can guide the clinician to provide effective and safe drug therapy in the individual patient. Monitoring can be used to confirm a plasma drug concentration which is above or below the therapeutic range, thus minimizing the time which elapses before corrective measures can be implemented in the patient Clinical pharmacokinetics emerged as a clinical discipline in the late 1960s and early 1970s. Clinical pharmacokinetic monitoring g( (CPM) helped many pharmacists to enter the clinical arena, but the focus was more on the pharmacists and tools. With the widespread acceptance of pharmaceutical care and patient-focused pharmacy, we need to see how clinical pharmacokinetics fits into the pharmaceutical care process. ١

2 According to one authority, we (pharmacists) provided CPM in the early years because pharmacy needed a mechanism to get out of the basement. CPM helped to justify our entry into the clinical arena. Likewise, according to another, many of us had the climbing the mountain because it s there mentality. Because the results of drug assays were available and we knew how to use and apply the appropriate pharmacokinetic equations, we climbed our mountain and provided CPM (TDM). WHY USE THERAPEUTIC DRUG MONITORING? The success of any fixed dosing regimen most often is based on the patient's clinical response to the drug. Fixed dosing regimens are designed to generate plasma drug concentrations (PDC) within a therapeutic range, ie, achieve the desired effect while avoiding toxicity. ٢

3 FOR WHICH DRUGS? Therapeutic drug monitoring (TDM) becomes important when: a) the drug has a narrow therapeutic-toxic range, b) there is a large variability in pharmacokinetic i parameter values between patients, c) the therapeutic effect is not readily assessed (e.g. antibiotics) or clinical symptoms are to be avoided (e.g. seizure). d) there is a direct relationship between Cp or concentration in other biological sample (e.g. saliva) and pharmacological effect, e) the expected or desired therapeutic effect is not observed Example Drugs Aminoglycosides such as gentamicin and tobramycin (0.5-8 mg/l) Digoxin ( (???) µg/l) Phenytoin (10-20 mg/l) Theophylline (10-20 mg/l) Cyclosporine ( mg/l) ٣

4 TDM Procedure Pharmacist and Physician develop initial dosing recommendations and target t concentrations Information required 1 Patient - age, weight, sex, height, smoker or not,.. 2 Clinical - clinical status (renal creatinine clearance, cardiac, liver, etc.) TDM Procedure contd... Calculate initial loading g( (and maintenance dose) and make recommendation Organize sample collection and analysis ٤

5 TDM contd... Sample Collection Accurate timing required Evaluate result pharmacokinetically Recalculate dosing regimen Organize further samples if required Population data Average values for V, Clearance etc. derived from large groups of patients. Where appropriate, these are quoted as per Kg body weight. Adjustments t may be made for characteristics such as smoking and certain disease states. Individual data Values for V, Clearance etc calculated from measured blood concentrations following the application of a known dose of the drug to the individual patient in question. ٥

6 New patient Determine body weight and any other relevant characteristics (Smoker, Cirrhosis, Renal failure etc) Calculate a dosage regime on basis of population data Apply this regime to the patient? Take blood samples (Therapeutic Drug Monitoring - TDM ) and note clinical state of patient If necessary, re-calculate dosage on basis of individualised data. Patient Monitoring Signs of Curing Signs of Adverse Reaction Physician Reassessment Pharmacist Modify Dosing Patient Monitoring Curing Termination of the Treatment ٦

7 Therapeutic failure of Phenobarbital Patient:??????? Chief Complaint: Seizures Pertinent History: Diagnosed as epileptic 6 months prior to presentation. Patient was suffering from severe cluster seizures. Response to phenobarbital was initially but 6 months into therapy, the patient has begun seizuring again. Drug of interest: Phenobarbital Dosing Regimen: 4.1 mg/kg every 12 hours orally. Duration of current regimen: 6 months. Phenobarbital concentrations at 3 months (baseline) were 35 mg/ml (peak) and 31mg/ml (trough). Elimination half-life at that time was 40 hours Recommendation: Increase phenobarbital dose to 7.5 mg/kg every 12 hours (4.5 mg/kg x 30 mg/ml / 18 mg/ml), targeting a peak concentration of 30 mg/ml. Retest at new steady-state (which will only take 3 to 5.5 days in this patient.) Follow-up: The dose was increased to 6.5 mg/kg. Drug concentrations one month later were 33 mg/ml (peak) and 29 mg/ml (trough). Patient has been seizure free for six months. Although bromide therapy could have been started in this patient, the increase in phenobarbital concentration was easier and as effective, leaving bromide available should this patient's disease get worse. ٧

8 Aminoglycoside and intensive fluid therapy Patient:???????? Chief Complaint: Peritonitis and bacteremia secondary to prostatic abscess Pertinent History: Surgical correction of prostatic abscess. Drug samples collected 24 hours postoperatively. Other drugs: Antiemetics (metoclopramide); intensive fluid therapy. Drug of interest: t Gentamicin i Dosing Regimen: 4 mg/kg IV every 24 hours Duration of current regimen: 24 hours Patient Response: Febrile, non-responsive Drug elimination half-life: 2.4 hrs Volume of distribution: 0.45 l/kg Predicted Peak concentration: 10 mg/ml Trough Concentration: non-detectable Recommendation: Double the dose to target 20 mg/ml (assuming an MIC of 1 to 2 mg/ml) and maintain current 24 hour dosing interval. Follow-up: Patient condition remained critical for two more postoperative days but then began progressive improvement. Patient was discharged 10 days postoperatively. ٨

9 Advantages of TDM 1) Facilitates t rapid determination ti of of the appropriate dosing regimen. 2) Evaluates existing dosage regimen. 3) Protects against drug toxicity. 4) Distinguishes between PK and PD causes of therapeutic failure. In Gallup's annual Honesty and Ethics poll, expanded this year to include nurses and 19 additional occupations not previously rated, nearly three-quarters of Americans, 73%, deem nurses' honesty and ethics as either very high or high, putting them at the top of the list. Pharmacists remains the top-rated t profession among occupations previously measured over the past 22 years; however, with a combined high/very high rating of 69%, they trail nurses on the new, expanded list by four percentage points. These are the Top Five professions and occupations considered most honest by the American public: Nurses 73%, Pharmacists, 69% Veterinarians, 63% Medical Doctors, 58% ٩

10 ١٠