Tuğba GÜMÜŞTAŞ, Mehmet MELLİ, Nihan KÜÇÜK

Antibiyotik Tedavisinde Farmakokinetik/Farmakodinamik Yaklașımın Önemi

Enfeksiyon hastalıklarının tedavisinde antibiyotiklerin uygun olmayan dozlamı bakterilerde direnç gelișimine ve buna bağlı olarak dirençli bakteriler ile yeni enfeksiyonların gelișmesine neden olmaktadır. Bu durum en-feksiyon hastalıkların tedavisinde büyük bir sorun olușturmaktadır.Antimikrobiyal tedaviye cevabı belirleyen farmakodinamik (PD) ve farmakokinetik (PK) ilkelerin anlașılması ve beraber değerlendirilmesi, tedavide uygulanan doz rejimlerinin uygun șekilde düzenlenmesini sağlar.Antibiyotik etkililiğini tahmin etmek için yaygın olarak kullanılan üç PD/PK parametre; 1) maksimum serum konsantrasyonunun (Cmaks), minimum inhibitör konsantrasyona (MİK) oranı (Cmaks/MİK), 2) plazma kon-santrasyonuna karșı zaman eğrisinde eğri altında kalan alan (EAA) ile MİK arasındaki oran (EAA/MİK) ve 3) an-tibiyotik plazma konsantrasyonunun MİK değerinin üzerinde olduğu süredir (T>MİK).PK/PD yaklașıma göre antibiyotikler; 1) konsantrasyon bağımlı etki gösterenler (aminoglikozidler, florokino-lonlar vs.), 2) zaman bağımlı etki gösterenler (beta-laktamlar, glikopeptidler vs.) șeklinde iki ana gruba ayrıl-maktadırlar. Günlük dozun; birinci grupta tek doz halinde, ikinci grupta ise bölünmüș dozlar halinde verilme-sinin daha etkili olduğu gösterilmiș ve bu durum kliniğe bașarılı bir șekilde yansıtılmıștır.Doz rejimlerini sadece PD parametresi olan MİK değ eri ile değil PK/PD yaklașımı ile belirlemek; bașarılı bakteri eradikasyonu sağladığı, toksisiteyi azalttığı, dirençli sușların olușma olasılığını azalttığı ve sonuç olarak klinik bașarıyı arttırdığı için son yıllarda tedavi yaklașımlarında göz önünde bulundurulmaktadır. Bu derlemede, en-feksiyon hastalıklarının tedavisinde PK/PD ilkelere göre antibiyotik kullanımının klinik yansımaları hakkında bilgi verilmiștir.

Importance of Pharmacokinetic/Pharmacodynamic Concept in Antibiotic Therapy

Inappropriate dosing of antibiotics used in the treatment of infectious diseases leads to the emergence of bacterial resistance which in turn, gives rise to the development of new infections with these resistant bacte-ria. This issue constitutes the major problem in the treatment of infectious diseases. The recognition and the co-evaluation of the principles of pharmacodynamics (PD) and pharmacokinetics (PK) determining the treatment response to antimicrobial therapy provides the proper arrangement of the dosing regimens used in the treatment. The three widespreadly used PD/PK parameters for the prediction of antibiotic efficacy are; (1)the ratio of maximum serum concentration (Cmax) to minimum inhibitory conncentration(MIC) (Cmax/MIC), (2) the ratio of the area under the plasma concentration versus time curve (AUC) to MIC (AUC/MIC), and (3) the duration of the dosing interval that plasma concentrations exceed the MIC value (T>MIC). According to PD/PK approach, antibiotics are classified as; 1) concentration-dependent (aminoglycosides, flu-oroquinolones, etc.), and 2) time-dependent (beta-lactams, glycopeptides, etc.). It is demonstrated that the antibiotics in the first group act better when the daily dose is given at a single dose, whereas the antibiotics in the second group act better when the daily dose is given in divided doses. The determination of dosing regimens by the way of PD/PK approach instead of the MIC value only, has been considered recently in the treatment modalities since it enables successful eradication of bacteria, reduces toxicity, alleviates the likelihood of the generation of resistant strains and consequently increases the clinical success rate. In this review, clinical implications of antibiotic use according to PK/PD principles in the treat-ment of infectious diseases have been discussed.

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