Oleh Admin Kalbe Medical pada May 12, 2017 07:30

Terapi Levofloxacin untuk Cystic Fibrosis

Pada pasien-pasien dengan cystic fibrosis (CF), terjadi peningkatan bersihan berbagai antibiotik seperti aminoglikosida dan beberapa antibiotik beta-laktam, sehingga diperlukan dosis antibiotik yang lebih tinggi. Levofloxacin merupakan antibiotik yang dieliminasi sebagian besar di ginjal dan memiliki penetrasi yang baik pada organ paru dan pada biofilm Pseudomonas aeruginosa (PA). Namun, dahulu masih dipertanyakan apakah terdapat perbedaan pada profil farmakokinetik dan farmakodinamik levofloxacin pada pasien-pasien dengan CF. Pada studi “Levofloxacin Pharmacokinetics in Adult Cystic Fibrosis”, dilakukan penelitian mengenai hal tersebut.

Studi dilakukan dengan pemberian levofloxacin 500 mg per hari pada 18 pasien dengan eksaserbasi pulmonal ringan sampai sedang selama 14 hari. Pada studi tersebut didapatkan bahwa pasien-pasien dengan CF memiliki kemiripan dengan pasien-pasien non-CF terhadap levofloxacin dalam hal area under the curve for 24h (AUC24), total clearance, volume of distribution, maximum serum concentration, dan eliminination half-time. Namun, terdapat kekurangan di mana pada pasien-pasien dengan CF yang diberikan levofloxacin, ternyata masih terdapat kekurangan yaitu dibutuhkan waktu yang lebih lama untuk mencapai kadar serum maksimum levofloxacin serta pada pemeriksaan sputum terhadap PA, sampel dari pasien-pasien tersebut gagal menunjukkan penurunan densitas dari PA pada sputum. Berdasarkan studi ini dapat disimpulkan bahwa dosis standar dari levofloxacin tidak efektif dalam mengobati pasien-pasien dengan CF.

Untuk menjawab tantangan di atas, baru-baru ini diluncurkan studi terbaru yang dilakukan untuk menentukan design dan karakteristik dari levofloxacin dan ciprofloxacin inhalable dry powder yang dikombinasikan dengan mukolitik berupa acetylcysteine dan dornase alfa sebagai terapi infeksi paru pada pasien-pasien dengan CF. Bahan-bahan yang digunakan pada pembuatan dry powders for inhalation ini mendapatkan perlakukan berupa proses miconization.

Hasil dari proses tersebut ialah perubahan struktur levofloxacin menjadi amorf dan perubahan mass median aerodynamic diameter dari levofloxacin yang membuat permeabilitas dari levofloxacin pada paru lebih tinggi. Dengan demikian, dapat disimpulkan bahwa proses micronization tersebut dapat menghasilkan sediaan inhalasi antibiotik dan mukolitik dry powder yang dapat menjawab tantangan terapi infeksi paru pada pasien-pasien dengan CF. Untuk dapat mengkonfirmasi hal itu, diperlukan penelitan lebih lanjut. (AHA)

Image : Ilustrasi
Referensi:
1.Lee CKK, Boyle MP, West MD, Noschese M, Zeitlin PL. Levofloxacin pharmacokinetics in adult cystic fibrosis. Chest. 2007;131(3):796-802.
2.Akdaq CY, Sahin S, Bitiini F, Baldicci AG, Montanari S, Vural I, Oner I. Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients. Drug Dev Ind Pharm. 2017 Apr 19:1-35. doi: 10.1080/03639045.2017.1318902.

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