ABSTRACT
OBJECTIVE： To establish a method for blood concentration determination of Fentanyl buccal tablet in Beagle dogs， and to study its pharmacokinetics. METHODS： A total of 6 Beagle dogs were given Fentanyl buccal tablet 1 tablet （675 μg/tablet， buccally）. The blood samples were collected 2， 5， 10， 15， 30， 45， 60， 90， 120， 240， 360， 480， 720 min after administration. After precipitated by methanol， LC-MS/MS method [the determination was performed on Agilent C18 column with mobile phase consisted of methanol-0.02％ formic acid aqueous solution （95 ∶ 5， V/V） at the flow rate of 0.5 mL/min. The sample size was 5 μL and the column temperature was 30 ℃. Mass spectrometric conditions： electrospray ionization source in the multiple reaction monitoring mode was used to detect ions， fentanyl citrate： m/z 337.1→188.0； carbamazepine （internal standand）： m/z 237.1→194.1] was used to determine the blood concentration of fentanyl citrate； the pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS： The linear range of fentanyl citrate were 1.0-325.0 ng/mL（r＝0.998）； inter-day RSDs of precision test were lower than 5％ （n＝6）， and intra-day RSDs were lower than 6％ （n＝3）； average recoveries were （94.65±6.32）％-（99.21±3.24）％ （n＝6）. RSDs of matrix effect was lower than 15％ （n＝6）； RE of stability tests were within ±6.2％ （n＝3）. The pharmacokinetic parameters of Fentanyl buccal tablet in Beagle dogs included that tmax was （32.5±6.1） min； t1/2 was （211.8±47.4） min； cmax was （40.3±1.9） ng/mL； CLz/F was （0.006±0.001） L/（min·kg）； AUC0-720 min was （7 564.0±1 576.7） ng·min/mL（n＝6）. CONCLUSIONS： The method is simple， feasible and accurate. Fentanyl buccal tablet have good fast-release and slow-release biphasic release characteristics in Beagle dogs.
ABSTRACT
Objective To investigate the changes and significance of serum inflammatory factors in coronary heart disease (CHD) patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) ,and the treatment effects of continuous positive airway pressure (CPAP).Methods A total of 76 CHD patients in Renmin Hospital of Wuhan University from October 2007 to October 2008 were enrolled.Polysomnography (PSG) was performed in these CHD patients to identify if they were complicated by OSAHS.The levels of inflammatory factors including TNF-α, IL-6, high sensitive C-reactive protein (hs-CRP) in serum were determined in the CHD patients and 23 normal subjects.The CHD patients with mederate-severe OSAHS (AHI≥ 15 episodes/hour) were treated by Auto-CPAP for 3 months and all parameters above were measured again.Results There were 41/76 (53.9%) of CHD patients had mederate-severe OSAHS and were treated with CPAP.The levels of TNF-ct,IL-6 and hs-CRP were significantly higher in the CHD patients than those in the normal controls (all P <0.01) ,and were significantly higher in moderate-severe OSAHS patients than those in the non-OSAHS CHD patients.Auto-CPAP ventilation significantly decreased the levels of inflammatory factors in the CHD patients with moderate-severe OSAHS.Conclusions An obvious proinflammatory state is detected in CHD patients ,and is aggravated with OSAHS.CPAP is a useful treatment for CHD patients with mediate to severe OSAHS.