OBJECTIVE:To determine the pharmacokinetics and relative bioavailability of oxetacillin and sulbactam in oxetacillin-sulbactam tablets.METHODS:20healthy male volunteers were randomly divided into2groups.In a crossover de?sign,a single oral dose of two tablets of domestic oxetacillin-sulbactam tablets or imported Tai Ba Meng LBL 500 tablets(one tablet of the two formulations contains oxetacillin250mg,sulbactam250mg)were given,then the drug concentrations in plas?ma were assayed by RP-HPLC.RESULTS:The pharmacokinetic parameters of oxetacillin in domestic and imported tablets were as follows:T max were(1.04?0.26)h and(1.10?0.28)h;C max were(5.16?1.30)mg/L and(5.25?1.21)mg/L;AUC 0～∞ were(13.30?3.12)mg/(h?L)and(13.33?3.53)mg/(h?L)respectively.The pharmacokinetic parameters of sulbactam in domestic and imported tablets were as follows:T max were(0.80?1.0)h and(0.81?0.17)h,C max were(5.73?1.44)mg/L and(5.70?1.46)mg/L,AUC 0～∞ were(13.25?2.41)mg/(h?L)and(13.28?2.26)mg/(h?L)respectively.CONCL_ USION:Domestic oxetacillin-sulbactam tablets and imported Tai Ba Meng LBL 500 tablets were bioequivalent.

Objective:To explore the clinical manifestations and characteristics of serum adrenal cortex hormone spectrum in patients with adrenocortical hypercortisolism with different pathological types of adrenal adenoma.Methods:A retrospective analysis was conducted on 68 patients with adrenal Cushing's syndrome who underwent surgical treatment in the Department of Endocrinology and/or Urology, Peking University First Hospital from January 2018 to June 2022. Among them, 12 patients had obvious eosinophilic changes in pathology(eosinophilic group), and 56 patients had no obvious eosinophilic changes(non-eosinophilic group). Among eosinophilic group, one male and 11 females, age(49.83±9.87) years old, body mass index (BMI)(25.86±3.21) kg/m 2, systolic blood pressure (140.25±20.72)mmHg(1 mmHg=0.133 kPa), diastolic blood pressure(91.00±14.87)mmHg, 7 cases were overt Cushing's syndrome. Among non-eosinophilic group, 14 males and 32 females, age(52.91±10.82) years old, BMI (26.06 ± 3.57) kg/m 2; ystolic blood pressure (142.13±16.71) mmHg, diastolic blood pressure (83.63±11.41) mmHg; 16 cases of overt Cushing's syndrome. There was no statistically significant difference in the above indicators between the two groups ( P>0.05).In terms of laboratory tests, 0: 00 cortisol levels in the eosinophilic group and non-eosinophilic groups were 14.95(5.93, 23.2) ng/dl and 6.69(4.07, 11.35) ng/dl ( P=0.044), the cortisol levels after 1mg dexamethasone inhibition test were 20.19(11.29, 26.92) ng/dl and 5.94(2.68, 12.90) ng/dl ( P=0.005), and 8: 00, 16: 00, and 0: 00, ACTH levels were 2.08 (1.02, 2.90) pg/ml and 8.37(2.30, 11.67) pg/ml ( P=0.006), 1.22(1.00, 3.20) pg/ml, and 4.22(1.80, 6.33) pg/ml ( P=0.012), 0.65 (0, 2.63) pg/ml, and 2.76(1.44, 5.57) pg/ml( P=0.023), serum triglyceride were 1.92(1.31, 2.50) mmol/L and 1.31(1.04, 1.80) mmol/L ( P=0.026), and the differences were statistically significant. In terms of target organ damage, there were 6 cases and 10 cases ( P=0.017) in the eosinophilic group and non eosinophilic group with ventricular wall hypertrophy, 1 case and 0 cases( P=0.030) in the aortic dissection group, and 4 cases and 5 cases ( P=0.024) with four or more types of target organ damage, respectively, with statistically significant differences. Two groups of preoperative serum adrenal cortex hormone profiles were detected by liquid chromatography tandem mass spectrometry. The differences in adrenal cortex hormone profiles and hormone ratios between the two groups were compared. Age, gender, and statistically significant indicators were included in a multivariate logistic regression model to analyze the correlation between each indicator and eosinophilic changes. Results:Adrenal cortical hormone profile of the two groups showed that the serum estrone levels in the eosinophilic group and non-eosinophilic group were 20.27(13.49, 39.81) pg/ml and 12.59(8.08, 21.18) pg/ml ( P=0.034), and 11-hydroxyandrostenedione levels were 692.34(536.19, 1 049.66) pg/ml and 1 157.60(710.78, 1 539.30) pg/ml( P=0.026), with statistically significant differences; There were no statistically significant difference in the expression levels of other hormones ( P>0.05). In terms of hormone ratio, the estradiol/testosterone ratios in the eosinophilic and non eosinophilic groups were 0.14(0.08, 0.62) and 0.04(0.01, 0.09)( P=0.008), the estrone/androstenedione ratios were 0.06(0.05, 0.12) and 0.04(0.03, 0.06)( P=0.007), the 11-hydroxyandrostenedione/androstenedione ratios were 2.26(1.30, 2.69) and 4.03(2.48, 5.25)( P=0.008), the estriol/estrone ratios were 0.10(0.03, 0.29) and 0.25(0.12, 0.51)( P=0.016), the estriol/estradiol were 0.22(0.03, 0.30) and 0.33(0.12, 0.73)( P=0.032), and the differences were statistically significant. The results of multivariate analysis showed that estrone ( OR=1.04, 95% CI 1.01-1.07, P=0.009) and estrone/androstenedione ( OR=25 008 670.29, 95% CI 8.45-74 015 852 572 024.10, P=0.025) were independently associated with eosinophilic pathology. Conclusions:Adrenocortical hypercortisolism patients with eosinophilic pathology have higher levels of serum cortisol secretion, more pronounced inhibition of the hypothalamic pituitary adrenal axis, more significant metabolic disorders and target organ damage, and higher production of estrone.