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Pertemuan II Farmakokinetika Klinik Tunggul AP, M.Sc., Apt.

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Presentasi berjudul: "Pertemuan II Farmakokinetika Klinik Tunggul AP, M.Sc., Apt."— Transcript presentasi:

1 Pertemuan II Farmakokinetika Klinik Tunggul AP, M.Sc., Apt.

2 Dosis yang diberikan (Resep) Dosis yang diminum Kadar Di Tempat Kerja Intensitas Efek Farmakologik (Respon Penderita) Faktor-faktor farmakokinetika Absorpsi (jumlah dan kecepatan) Distribusi (ukuran dan komposisi tubuh, distribusi dalam cairan2 tubuh, ikatan protein Eliminasi Faktor-faktor farmakodinamik Interaksi obat-reseptor Keadaan fungsional jaringan Mekanisme homeostatik Sensitivitas reseptor/jaringan Compounding and Dispensing Kepatuhan Penderita Kondisi fisiologik Kondisi patologik Faktor genetik Interaksi obat Toleransi

3 PEMILIHAN OBAT – INDIKASI TERAPETIK SAMA –PROFIL FARMAKOKINETIKA BERBEDA – DIDASARKAN PADA DIGNOSIS YANG TEPAT – FARMAKODINAMIK DAN KADAR TERAPETIK – F.KINETIKA OBAT – KONDISI PATO-FISIOLOGIS – RIWAYAT PENGOBATAN SEBELUMNYA – TERAPI TUNGGAL / GANDA – ALERGI / KEPEKAAN – DAFTAR OBAT ESENSIAL – HARGA – KENYAMANAN & KEPATUHAN

4 Prinsip pendosisan (dosage regimen) Berapa banyak, berapa sering, berapa lama ? Initial dose, maintainance dose, discontinuing the dose

5 Management of therapy Multiple drug therapy Convenience of regimen Compliance of patient Other Factors Route of administration, Dosage form, Tolerance- Pharmacogenetics- Drug interactions, Cost Activity-Toxicity Therapeutic window Side effects Toxicity Concentration-response relationship Pharmacokinetics Absorption Distribution Metabolism Excretion Clinical Factors State of patient Age, weight,Condition being treated, Existence of other disease states Dosage Regimen

6 RANCANGAN ATURAN DOSIS ACTIVITY –TOXICITY TERAPEUTIC WINDOW SIDE EFFECT TOXICITY CONCENTRATIONS-RESPONS RELATIONSHIPS

7 PHARMACOKINETICS ABSORPTION DISTRIBUTION METABOLISM EXCRETION

8 CLINICAL FACTORS CLINICAL FACTORS STATE OF PATIENT : AGE, WEIGHT,GENDER, NUTRITIONAL, CONDITION BEING TREATED, RENAL DYSFUNCTION, LIVER DEASESE, CONGESTIVE HEART FAILURE EXISTENCE OF OTHER DESEASE STATES MANAJEMEN OF THERAPY : MULTIPLE DRUG THERAPY CONVENIENCE OF THERAPY COMPLIANCE OF PATIENT

9 OTHER FACTORS -ROUTE OF ADMINISTRARION -DOSAGE FORM -TOLERANCE -PHARMACOGENETICS -DRUG INTERACTIONS : ENVIROMENTAL FACTORS (SMOKING) -CELL TARGET (RECEPTOR) SENSITIVITY -COST

10 A pharmacokinetic model is applied and clinical judgement is used Drug concentrations are determined Patient assessments are performed Drug is administered Dosage schedule is designed to reach a target plasma concentration A drug is selected A diagnosis is made If dosage adjustment necessary Figure Process for reaching dosage decisions with therapeutic drug monitoring

11 PENILAIAN RESPON PENDERITA RESPON POSITIF : TERUS RESPON KURANG : - EVALUASI DOSIS & INTERVAL ; INTERAKSI -EVALUASI FARMAKODINAMIK -KEPATUHAN RESPON NEGATIF : STOP

12 Population versus Individual Values for PK Parameters Value of PK Parameter # of People Population values represent average values rather than the value for YOUR patient. Individual values represent the values in YOUR patient, but they have to be determined in YOUR patient. Widely Available PK Values Rarely Available PK Values

13 Population versus Individual Values for PK Parameters If available, of course use individual values for PK parameters. You will nearly always have to settle for population values for PK parameters.

14 Decide whether LD is required and, if so, calculate LD.

15 Can you afford to wait 4t 1/2 s to obtain [D] P SS ? YesNo Do not give LD.Calculate LD.

16 Capacity-Limited Metabolism (Also called “Zero Order Kinetics”) An infrequent, but important phenomenon Clearance is not constant with respect to [D] P because metabolizing enzymes are saturated at “therapeutic concentrations” Rate of drug elimination is fixed and cannot use clearance to calculate dosage regimen For such drugs, daily dose should not exceed fixed rate of elimination

17 A dosage regimen may need to be adjusted if plasma clearance changes, for instance because of disease.

18 If drug is eliminated mostly by liver, no adjustment required. Adjusting Dosage Regimens in Patients with Renal Disease If drug is eliminated mostly by kidney, either: Re-evaluate need for drug and discontinue if possible Reduce dose Increase dosing interval Switch to drug eliminated mostly by liver Contoh: Vancomycin population pharmacokinetic Dosage nomogram of vancomycin

19 If drug is eliminated mostly by kidney, no adjustment required. Adjusting Dosage Regimens in Patients with Liver Disease If drug is eliminated mostly by liver, either: Re-evaluate need for drug and discontinue if possible Reduce dose Increase dosing interval Switch to drug eliminated mostly by kidney

20 HOW DO I DESIGN AND ADJUST A DOSAGE REGIMEN? Now you know!!

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