Population pharmacokinetics study of dexmedetomidine in Chinese adult patients during spinal anesthesia.

OBJECTIVES: The objectives of this study were to construct a population pharmacokinetics model for dexmedetomidine used in Chinese adult patients with spinal anesthesia and to identify the key factors affecting the pharmacokinetics of dexmedetomidine. METHODS: A total of 34 subjects (elderly group: n = 15; young group: n = 19) undergoing spinal anesthesia received dexmedetomidine with a loading dose of 0.5 µg×kg(-1) for 10 minutes, followed by a maintenance dose of 0.5 µg×kg-1×h(-1) for 50 minutes. Blood samples were collected until 10 hours after dosing. Laboratory and respiratory parameters, and dexmedetomidine concentrations were measured. A population pharmacokinetic model for dexmedetomidine was constructed using a nonlinear mixed effects model (NONMEM). RESULTS: Pharmacokinetics of dexmedetomidine can be described by a three-compartment model. The respective typical values for clearance (CL), V1, V2, Q2, Q3, and V3 were 0.883 L×min(-1), 17.6 L, 51.5 L, 2.37 L×min(-1), 0.517 L×min(-1), and 44.00 L. Alanine aminotransferase (ALT), age, and body weight were key factors affecting CL, V1, and V2, respectively. CONCLUSIONS: A three-compartment model can be used to describe the pharmacokinetics processing of dexmedetomidine for Chinese adult patients during spinal anesthesia. The population pharmacokinetic of dexmedetomidine was generally in line with results from previous studies.

[Effect of IL-10 on LOX-1 expression of peripheral blood monocytes in patients with acute coronary syndrome].

OBJECTIVE: To determine the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of peripheral blood monocytes in patients with acute coronary syndromes (ACS),and to further explore the effect of anti-inflammatory factor interleukin-10 (IL-10) on the expression of LOX-1. METHODS: Twenty-eight healthy controls and 28 ACS patients were enrolled in the study. The levels of IL-10 and tumor necrosis factor (TNF-alpha) were determined by enzyme-linked immunosorbnent assay(ELISA). The monocytes of peripheral blood in patients and controls were isolated and incubated with exogenous IL-10 (20 microg/L). The expression of LOX-1 protein and mRNA in the monocytes was examined by Western blot and reverse transcriptase PCR (RT-PCR). RESULTS: Compared with the healthy controls, the levels of serum IL-10 and TNF-alpha were significantly elevated in ACS patients (P<0.01). The expression of LOX-1 protein and mRNA was markedly upregulated in the isolated monocytes from ACS patients, which could be downregulated by IL-10 (20 microg/L, 3 h) (P<0.01). CONCLUSION: The effect of anti-inflammatory factor IL-10 on the atherosclerosis may be a new mechanism resulting in plaque stabilization via the decreased LOX-1 expression of peripheral monocytes in ACS patients.

[Proatherogenic effects of immune complexes of human oxLDL in vitro].

OBJECTIVE: To observe the effects of immune complexes (IC) prepared from human oxidized density lipoprotein (oxLDL) antibodies and human oxLDL on the foam cell forming and the macrophage activation, and to further uncover the possible mechanisms of immune complexes contributing to the atherosclerosis occurrence. METHODS: The immune complexes of human oxLDL and purified human oxLDL antibodies were added to culture U937 cells by protocols: polyethylene glycol-precipitated insoluble IC (PEG-IC) and IC immobilized by absorption to red blood cells (RBC-IC). With oxLDL as controls and heat-aggregated gamma globulin as an inhibitor of Fc gamma receptor, we measured the cholesterol ester, total cholesterol of the cellular extracts, and quantified the secreted MMP-1 of supernatants from U937 cells. RESULTS: A significant increase of MMP-1 release [(0.769 +/- 0.030) ng/ml vs (0.513 +/- 0.034) ng/ml, P < 0.01] and a higher level of cholesterol ester accumulation [(20.271 +/- 1.668) microg/mg protein vs (17. 226 +/- 1.298 ) microg/mg protein, P < 0.05] in U937 cells incubated with RBC-IC were observed, compared with those incubated with RBC-oxLDL. However, the above quantative difference between the cholesterol ester accumulation induced by oxLDL and insoluble PEG-IC was even more striking, and cholesterol ester accumulation was dosage-dependent. Heat-aggregated gamma globulin (10 mg/ml) as an inhibitor of Fc gamma receptors competitively inhibited cholesterol ester accumulation and decreased PEG-IC stimulating MMP-1 secretion to 71%. CONCLUSION: Immune complexe of ox-LDL can transform macrophages into foam cells and activted macrophages. The immunological function of oxLDL is involved in the process of atherosclerosis occurrence.