Hyo-Jin Byon1, Byung-Moon Choi2, Ji-Yeon Bang2, Eun-Kyung Lee3, Sang-Seok Lee4, Gyu-Jeong Noh5. 1. Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea. 2. Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 3. Department of Statistics, Ewha Womans University, Seoul, Korea. 4. Department of Anesthesiology and Pain Medicine, Sanggye Paik Hospital, University of Inje College of Medicine, Seoul, Korea. 5. 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.
Abstract
PURPOSE: 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. FINDINGS: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. IMPLICATIONS: No significant difference was found in the mean MAC between generic and original sevoflurane. ClinicalTrials.gov identifier: NCT01096212.
RCT Entities:
PURPOSE: 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 ureanitrogen, 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. FINDINGS: 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. IMPLICATIONS: No significant difference was found in the mean MAC between generic and original sevoflurane. ClinicalTrials.gov identifier: NCT01096212.
Authors: Mary Cooter; Katherine Ni; Jake Thomas; Dhanesh K Gupta; Thomas J Hopkins; Timothy E Miller; Michael L James; Miklos D Kertai; Miles Berger Journal: Br J Anaesth Date: 2019-11-01 Impact factor: 9.166
Authors: Rakesh V Sondekoppam; Karim H Narsingani; Trent A Schimmel; Brie M McConnell; Karen Buro; Timur J-P Özelsel Journal: Can J Anaesth Date: 2020-08-18 Impact factor: 6.713