Amikasin Infus Intravena: Kajian Farmakokinetika/Farmakodinamika, Efektivitas dan Toksisitas pada Pasien Rawat Inap Dewasa di RSUP Dr. Sardjito Yogyakarta

ESTI DYAH UTAMI, Prof. Dr. apt. Ika Puspitasari, M.Si.; dr. Rizka Humardewayanti Asdie, Sp.PD-KPTI; Prof. Dr.rer.nat. apt. RR. Endang Lukitaningsih, M.Si.

2024 | Disertasi | DOKTOR ILMU FARMASI

Amikasin merupakan antibiotik concentration-dependent yang memiliki indeks terapi sempit. Pemberian amikasin IV direkomendasikan secara infus 30-60 menit. Durasi infus dapat mempengaruhi kadar obat dalam darah. Indeks farmakokinetika/farmakodinamika (FK/FD) yaitu rasio Cmax/MIC amikasin dilaporkan berkorelasi dengan kemanjuran. Penelitian bertujuan mengetahui pola dan rasionalitas penggunaan amikasin, mengembangkan metode Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) untuk penetapan kadar amikasin, mengkaji parameter FK/FD amikasin infus IV 30 menit dibandingkan 60 menit, serta hubungannya dengan efektivitas dan toksisitas pada pasien rawat inap dewasa di RSUP Dr. Sardjito Yogyakarta.

Penelitian tahap I dilakukan dengan pengambilan data rekam medik pasien tahun 2020 dengan terapi amikasin. Tahap II dilakukan optimasi dan validasi metode LC-MS/MS, meliputi uji selektivitas, carry over, linearitas, LLOQ, akurasi-presisi, dilution integrity, serta stabilitas. Tahap III merupakan studi prospektif pada subyek dengan terapi amikasin infus 30 atau 60 menit yang memenuhi kriteria inklusi. Evaluasi efektivitas berdasarkan outcome klinik, mortalitas, dan length of stay. Monitoring tanda toksisitas berdasarkan data klinik dan laboratorium. Parameter farmakokinetika (Cmax dan Cmin) amikasin dihitung estimasinya dengan rumus farmakokinetika, dan pengukuran real kadar dengan LC-MS/MS. 

Hasil penelitian menunjukkan amikasin mayoritas digunakan dalam kombinasi antibiotik, terapi definitif, dosis <15>

Amikacin is a concentration-dependent antibiotic that has a narrow therapeutic index. Administration of IV amikacin is recommended as a 30-60 minute infusion. The duration of infusion may affect the blood drug levels. The pharmacokinetics/pharmacodynamics (FK/FD) index, namely amikacin Cmax/MIC ratio, is reported to correlate with efficacy. The study aimed to determine the pattern and rationality of amikacin use, develop a Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) method for determining amikacin levels, assess PK/PD parameters of amikacin IV infusion 30 minutes compared to 60 minutes, and its relationship with effectiveness and toxicity in adult inpatients at Dr. Sardjito Hospital Yogyakarta.

Phase I research was conducted by collecting medical record data of inpatients in 2020 with amikacin therapy. Phase II was carried out optimization and validation of the LC-MS/MS method, including selectivity, carry over, linearity, LLOQ, accuracy-precision, dilution integrity, and stability tests. Phase III was a prospective study in subjects with 30 or 60 minutes of amikacin infusion therapy who met the inclusion criteria. Evaluation of effectiveness based on clinical outcomes, mortality, and length of stay. Monitoring for signs of toxicity based on clinical and laboratory data. Pharmacokinetic parameters (Cmax and Cmin) of amikacin were estimated by pharmacokinetic formula, and actual levels were measured by LC-MS/MS.

The results showed that the majority of amikacin was used in combination antibiotics, definitive therapy, dose <15>

Kata Kunci : Amikasin, Infus Intravena, Farmakokinetika/Farmakodinamika, Efektivitas, Toksisitas