title: An Open-label Comparison of a New Generic Sevoflurane Formulation With Original Sevoflurane in Patients Scheduled for Elective Surgery Under General Anesthesia.
abstract: OBJECTIVE
  To compare the stability, effectiveness, and safety profiles of a new generic sevoflurane with those of the original sevoflurane formulation in patients undergoing elective surgery.
  
  
  METHODS
  An accelerated 3-month storage test was performed to evaluate the compositional changes in generic sevoflurane stored in glass bottles. In addition, 182 patients were randomly allocated to receive generic (n = 89 [54 men and 35 women]; mean [SD] age, 49.9 [11.6] years) or original (n = 93 [61 men and 32 women]; mean [SD] age, 49.6 [11.1] years) sevoflurane at a gas flow of 3 L/min for approximately 3 hours. The mean minimum alveolar concentration (MAC) during sevoflurane anesthesia was evaluated, and gas samples for measuring compound A were collected from the inspiratory limb of the circuit at preset intervals. Blood samples for measuring serum inorganic fluoride were obtained at preset intervals (pharmacokinetic group: generic/original sevoflurane = 45/46). Renal biomarkers, such as N-acetyl-β-glucosaminidase, α- and π-glutathione-S-transferase, albumin, urine protein and osmolality, serum creatinine and osmolality, creatinine clearance, and blood urea nitrogen, were measured at preset intervals (renal biomarker group: generic/original sevoflurane = 44/47). Adverse reactions were monitored for 72 hours after discontinuation of sevoflurane use.
  
  
  RESULTS
  Generic sevoflurane contained in glass bottles was stable for 3 months. The mean MAC was similar for generic and original sevoflurane (median [range], 0.93 [0.67-1.29] vs 0.94 [0.63-1.5] vol%). Adverse event rates were similar (90.3% vs 84.3%), as were the AUClast of inorganic fluoride (333.7 [112.7-1264.7] vs 311.9 [81.5-1266.5] hours·μmol/L) and compound A (51.8 [6.3-204.5] vs 55.3 [10.8-270.6] hours·ppm). Biomarkers associated with renal injury were not significantly different between the 2 formulations.
  
  
  CONCLUSIONS
  No significant difference was found in the mean MAC between generic and original sevoflurane. ClinicalTrials.gov identifier: NCT01096212.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Byon
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Byung-Moon
authors.initials: BM
authors.lastname: Choi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Bang
authors.affiliation: Department of Statistics, Ewha Womans University, Seoul, Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Sanggye Paik Hospital, University of Inje College of Medicine, Seoul, Korea.
authors.forename: Sang-Seok
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Department of Clinical Pharmacology and Therapeutics, Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address: nohgj@amc.seoul.kr.
authors.forename: Gyu-Jeong
authors.initials: GJ
authors.lastname: Noh
mesh_terms: D000328:Adult; D000368:Aged; D000768:Anesthesia, General / Q000379:methods*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000009:adverse effects; D001806:Blood Urea Nitrogen; D017558:Elective Surgical Procedures / Q000379:methods; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D000077149:Sevoflurane; D055815:Young Adult
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: compound A; effectiveness; generic sevoflurane; inorganic fluoride