Kasus Clinical Pharmacokinetic Kel. 1 Edit

CLINICAL PHARMACOKINETICSFARMASI KLINIK / APOTEKER B

KELOMPOK I (SATU)

SOAL

1. An 81-years-old woman was admitted to hospital with a

3 week history of increasing jaundice and pale faeces

and a 2-month history of darkening urine. The liver

function tests showed markedly raised serum total

bilirubin, ALP. and GGT with slightly elevated AST levels.

Her plasma albumin level and prothrombin time were

normal. A diagnosis of obstructive jaundice was made.

Comment on hepatic drug clearance in this patient !

JAUNDICE OBSTRUKTIF

• Hambatan aliran empedu yang disebabkan oleh

sumbatan mekanik menyebabkan terjadinya kolestasis

yang disebut sebagai ikterus obstruktif

• Aktifitas enzim alkalifosfatase akan meningkat dan ini

merupakan tanda adanya kolestasis.

• Penyakit hati kolestatik ditandai dengan akumulasi

substansi hepatotoksik, disfungsi mitokondria dan

gangguan pertahanan antioksidan hati.

PATOFISIOLOGI

• Feses biasanya menjadi pucat karena kurangnya bilirubin yang

mencapai usus halus.

• Ketiadaan garam empedu dapat menyebabkan malabsorpsi,

mengakibatkan steatorrhea dan defisiensi vitamin larut lemak

(A, D, K); defisiensi vitamin K bisa mengurangi level protrombin.

• Retensi bilirubin menyebabkan hiperbilirubinemia campuran.

Beberapa bilirubin terkonjugasi mencapai urin dan

menggelapkan warnanya.

Altered pharmacokinetic parameters

1. When hepatocytes are damaged Clint decreases hepatic clearance reduces

2. If the drug has a hepatic first-pass effect BA will increases

3. A simultaneous effect of (1) and (2) results in extremely large increases in Css for orally administered drugs

4. LBF decreases depresses hepatic drug clearance even further

5. The liver produces albumin and a-1-acid glycoprotein in the blood. The production of these proteins decline in patient with cirrhosis free fraction of drugs in the blood.

6. Since clearance decreases and Vd usually increases the t½ almost always increases.

Altered pharmacokinetic parameters

Determination of Child-Pugh Scores

• No single laboratory test to assess the liver function (not like

CLCr to measure renal function)

• The most common way to estimate the ability of the liver to

metabolize drug is to determine the Child-Pugh score for a

patient.

• The Child-Pugh score consists of five laboratory tests or clinical

symptoms. The five areas are serum albumin, total bilirubin,

prothrombin time, ascites, and hepatic encephalopathy

Determination of Child-Pugh Scores

Determination of Child-Pugh Scores

• Each of the symptom is given a score of 1

(normal) to 3 (severely abnormal), and the scores

for the five areas are summed.

• The Child-Pugh score for a patient with normal

liver function is 5, whereas for abnormal (hepatic

damage) is 15

Determination of Child-Pugh Scores

• A Child-Pugh score equal to 8–9 is grounds for a

moderate decrease (~25%) in initial daily drug

dose for agents that are primarily (≥60%)

hepatically metabolized,

• A score of 10 or greater indicates that a significant

decrease in initial daily dose (~50%) is required for

drugs that are mostly liver metabolized.

Determination of Child-Pugh Scores

• For example, the usual dose of a medication that

is 95% liver metabolized is 500 mg every 6 hours,

and the total daily dose is 2000 mg/d. For a

hepatic cirrhosis patient with a Child-Pugh score

of 12, an appropriate initial dose would be 50% of

the usual dose or 1000 mg/d. The drug could be

prescribed to the patient as 250 mg every 6 hours

or 500 mg every 12 hours.

KESIMPULAN

1. An 81-years-old woman was admitted to hospital with a

3 week history of increasing jaundice and pale faeces and

a 2-month history of darkening urine. The liver function

tests showed markedly raised serum total bilirubin, ALP.

and GGT with slightly elevated AST levels. Her plasma

albumin level and prothrombin time were normal. A

diagnosis of obstructive jaundice was made. Comment

on hepatic drug clearance in this patient !

KESIMPULAN

TES SKOR

Total Bilirubin 3

Serum Albumin 1

Waktu Protrombin 1

Ascites 1

Hepatik Encefalopati 1

CHILD-PUGH SCORE 7

PUSTAKA

1. E-book Applied Clinical Pharmacokinetics

2nd edition (2008)

SOAL

2. A single dose antibiotic tablet 250 mg is administered to a

man (32 years old; creatinine clearance 122 mL/min; 78 kg).

According to the references, its Vd isi 21% of body weight

and its elimination half-time 2 hours. Normally, 90% of the

dose is available in systemic. Urine excretion of the drug that

is not unchanged equal with 70% of absorbed dose.

a) Count the total clearance of this drug !

b) Determine renal clearance of this drug !

c) What is the most likely mechanism for renal clearance of this

drug !

KLIRENS TOTAL OBAT (ClT)

Klirens Total (ClT)

KLIRENS GINJAL (Clr)

atau

MEKANISME KLIRENS GINJAL

MEKANISME KLIRENS GINJAL

MEKANISME KLIRENS GINJAL

Laju filtrasi glomerulus diukur dengan menggunakan suatu obat

yang dieliminasi hanya dengan filtrasi (tidak direabsorpsi atau

disekresi). Contoh obatnya adalah inulin dan kreatinin. Oleh karena

itu, klirens inulin atau klirens kreatinin sama dengan laju filtrasi

glomerulus.

Klirens inulin = 125-130 ml/menit

Klirens kreatinin = 122 ml/menit

Klirens obat = 66,22 ml/menit

KESIMPULAN:

Karena klirens obat (Clr) lebih kecil daripada klirens inulin/kreatinin

maka mekanisme yang mungkin untuk klirens ginjal adalah obat

difiltrasi dan sebagian direabsorpsi.

PUSTAKA

1. E-book Applied Biopharmaceutics and

Pharmacokinetics 5th edition

SEKIAN & TERIMA KASIHFARMASI KLINIK / APOTEKER B