关键词: 重组人胰高血糖素类多肽-1(7-36), 单次皮下注射, 耐受性

Abstract: AIM: To estimate the safety and tolerance of recombinated human glucagon-like peptide-1(rh-GLP-1) (7-36) after subcutaneous injection of single dose of the drug in Chinese healthy volunteers. METHODS: The protocol was designed according to GCP and approved by ethics committee.All volunteers signed the informed consent.The volunteers were 18-45 years old and divided into 7 dosage groups.The clinical and laboratory tests were observed in order to evaluate the safety and tolerance of rhGLP-1 (7-36). RESULTS: All laboratory and clinical indexes of the subjects were within the normal range and qualifications were equilibrate before administration of the drug, so they were comparable.After administration of rhGLP-1 (7-36), the incidence of adverse events (nausea, vomiting) exceeded 50% in 0.30 mg group, so only 24 cases in 4 groups (0.10-0.30 mg) joined the phasa I clinical trial.After administration of the drug, the significant changes in laboratory tests were not seen, but adverse reactions such as dizziness, nausea and emesia in 10 cases (15 times) were found which might be related to the drug.They could be tolerable, were temporary response, and disappeared one hour after the administration.The ADR occurred mainly in the 0.25 mg and 0.30 mg groups (7 of 12 subjects), while the ADR in the low-dose groups (0.10, 0.20 mg) were only found for 3 cases.There were 10 cases with dizziness and nausea and 5 emesia among 15 ADR.There were no serious adverse events during the clinical trial. CONCLUSION: rhGLP-1(7-36) is safe and tolerable in Chinese healthy volunteers when the single dose under 0.20 mg is subcutaneously injected, and the most tolerable dose is 0.20 mg.When the dose is up to 0.25 mg or 0.30 mg, the incidence of ADR is higher.The mechanisms for ADR of the nausea and vomiting will be studied in future.

Key words: recombinated human glucagon-like peptide-1, subcutaneous injection in single dose, tolerance