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Effects of Rat Intestinal Flora on the Pharmacokinetic Parameters of Pyrazinamide and Its Active Metabolite Py- razinoic Acid / 中国药房
China Pharmacy ; (12): 412-417, 2021.
Article in Chinese | WPRIM | ID: wpr-873480
ABSTRACT
OBJECTIVE:To study the effects of rat intestinal flora on the pharmacokinetic parameters of pyrazinamide and its active metabolite pyrazinoic acid. METHODS :Totally 16 SD rats were randomly divided into trial group and control group ,with 8 rats in each group. Trial group was given mixed antibioticsstreptomycin sulfate+neomycin sulfate )intragastrically to construct pseudoaseptic rat model. After modeling ,both groups were given pyrazinamide intragastrically (150 mg/kg). Before and 0.167, 0.333,0.667,1,1.5,2,3,4,6,9 h after administration ,0.1 mL blood sample was collected from orbital venous plexus ,and 0.3 mL blood sample was collected from orbital venous plexus 12,24 h after administration. Using phenacetin as internal standard , LC-MS/MS method was adopted to determine the plasma concentration of pyrazinamide and pyrazinoic acid. The determination was performed on Agilent ZORBAX SB-Aq column with mobile phase consisted of 0.2% formic acid (containing 8 mmol/L ammonium acetate)-methanol(gradient elution )at the flow rate of 1 mL/min. The column temperature was set at 30 ℃,and sample size was 10 μL. The ion source was ESI and the temperature of ion source was 500 ℃. The collision gas was nitrogen and the pressure was 10 psi. The temperature of mass transfer interface was 100 ℃. The mass spectrum monitoring mode was multi reaction monitoring , and the collection mode was positive ion mode. The monitoring transition ion-pairs were m/z 124.0→79.0(pyrazinamide),m/z 125.1→79.1(pyrazinic acid )and m/z 180.0→110.2(internal standard ). The de-clustering potential and collision voltage were 55, 26 and 85 V,24,23 and 28 V,respectively. The pharmacokinetic parameters were calculated and compared by using DAS 2.1.1 software. RESULTS :The linear ranges of pyrazinamide and pyrazinoic acid were 25-5 000 ng/mL(r=0.997 6)and 100-12 500 ng/mL(r=0.999 0). The lower limits of quantification were 25 and 100 ng/mL,respectively. Intra-batch and inter-batch accuracy were 92.93%-100.50%,and RSDs of intra-batch and inter-batch precision and matrix effect tests were all lower than or equal to 8.42%(n=6 or n=3). Compared with control group ,tmax of pyrazinamide in trial group was prolonged significantly (P<0.01); there was no statistical significance in other pharmacokinetic parameters between 2 groups(P>0.05). CONCLUSIONS :The absorption of single dose pyrazinamide is delayed with the change of intestinal flora in rats.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: China Pharmacy Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: China Pharmacy Year: 2021 Type: Article