KONCENTRACIJE ITRAKONAZOLA I HIDROKSI-ITRAKONAZOLA NAKON ORALNE PRIMENE LEKA KOD ZDRAVIH LJUDI: UTICAJ POLA

  • Tijana Stanojković
  • Milijana Miljković
  • Nemanja Rančić Centre for Clinical Pharmacology; Medical Faculty Military Medical Academy, University of Defence, Belgrade, Serbia https://orcid.org/0000-0002-5122-8094
  • Aleksandra Kovačević
  • Viktorija Dragojević Simić
DOI: https://doi.org/10.5937/halo27-30859
Ključne reči: itrakonazol, hidroksi-hidroksiitrakonazol, koncentracije leka, zdravi ispitanici, pol

Sažetak


Cilj rada je bio da se ispita uticaj pola na koncentracije itrakonazola i hidroksi-itrakonazola u plazmi zdravih odraslih osoba nakon peroralne primene leka. Sprovedena je klinička farmakokinetska studija u kojoj je učestvovalo 22 odraslih zdravih muških ispitanika i 16 ženskih kod kojih je peroralno primenjen itrakonazol u jednoj dozi od 100mg. Uzorci krvi su uzeti pre primene leka, kao i u odgovarajućim vremenskim intervalima do 72 sata nakon toga. Koncentracije leka i metabolita su određivane primenom validirane metode tečne hromatografije sa masenom spektrometrijskom detekcijom, a njihovi farmakokinetski parametri korišćenjem Kinetica programa, verzija 5.0: Cmax,Tmax,PIK(0-72),PIK(0-∞),T1/2  i Ke.   
Kod ispitanica vrednosti medijane koncentracija i itrakonazola i hidroksi-itrakonazola su bile manje u odnosu na muškarce u toku celog posmatranog perioda. Takođe, izračunete vrednosti medijana parametara resorpcije – Cmax, PIK(0-72) i PIK(0-∞) su bile statistički značajno manje i za lek (p=0,005, 0,036 i 0,036) i za metabolit (p=0,004, 0,010 i 0,044) kod žena. Parametri eliminacije - T1/2  i  Ke se nisu razlikovali među polovima.
Žene su nakon peroralne primene leka u manjem stepenu izložene itrakonazolu i njegovom aktivnom metabolitu u odnosu na muškarce, kao rezultat manje bioraspoloživosti ovog leka, uključujući i intenzivniji presistemski metabolizam usled veće ekspresije i/ili aktivnosti izoforme enzima koji ga metaboliše, a što bi bilo neophodno potvrditi farmakogenomskim analizama.

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2021/04/27
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Vol. 27 Br. 1 (2021): Naučni časopis urgentne medicine Halo 194
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