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Purpose: Histamine dihydrochloride (HDC) injection has been approved in Europe for the treatment of adults with acute myeloid leukemia (AML), used in combination therapy with the T-cell-derived cytokine interleukin (IL-2).Despite years of clinical applications of HDC in Europe, no data is available for its safety and pharmacokinetics in Chinese individuals.The objective of this study was to determine the safety and pharmacokinetic properties of HDC in Chinese healthy volunteers (HVs).Methods: In this phase Ⅰ, single-center, open-label, randomized study, 20 Chinese HVs were randomized to receive a single dose of 0.5 or 1.0 center, open-label, randomized study, 20 Chinese HVs were randomized to receive a single dose of 0.5 or 1.0 mg HDC via a 10-minute subcutaneous injection.Whole-blood and urine samples were collected at designed time points after dosing.The plasma and urine concentrations of histamine and metabolite N-methyl histamine (NMH) were measured using a validated HPLC-MS/MS method.Pharmacokinetic parameters were estimated through noncompartmental procedures based on the concentration-time data.Adverse events (AEs) and evaluation of clinical laboratory tests were used to assess the safety profile.The pharmacokinetic profile for single-dose 1.0 mg HDC in Chinese HVs was compared with that in Western HVs.Findings: No severe AEs occurred in this study, and the severity of all AEs was of grade Ⅰ according to the Common Terminology Criteria for Adverse Events version 4.0.For the pharmacokinetic parameters of histamine at 0.5 and 1.0 mg dose levels, t1/2 was 0.50 and 1.02 h, respectively;Tmax was 0.15 and 0.14 h;mean Cmax was 26.59 and 71.01 nmol/L;AUC0-t was 8.35 and 20.43 nmol·h/L;AUC0-∞ was 9.61 and 22.69 nmol·h/L;accumulated amount excreted in urine within 24 h (Ae0-24h) was 125.93 and 145.52 nmol;maximum urine excretion rate (Rmax) was 21.85 and 38.94 nmol/h.For NMH at 0.5 and 1.0 mg dose levels, t1/2 was 0.58 and 0.66 h, respectively;Tmax was 0.28 and 0.26 h;mean Cmax was 17.01 and 23.54 nmol/L;AUC0-t was 7.72 and 17.08 nmol·h/L;AUC0-∞ was 9.01 and 19.62 nmol-h/L;Ae0-24h was 331.7 and 583.21 nmol;Rmax was 53.29 and 133.53 nmol/h.Implications: Both single-dose 0.5 and 1.0 mg HDC were safe and well tolerated in Chinese HVs, and the pharmacokinetics of HDC in Chinese HVs was characterized in this study.Asingle dose of 1.0 mg HDC had a more rapid but similar extent of absorption, a wider distribution, and a little more rapid elimination in Chinese HVs compared with Western HVs.Findings from this study support further clinical trials for HDC using in Chinese individuals.ChiCTR-ONC-13003954.