| Nitazoxanide (Nitazoxanide, NTZ) is belongs to the family of thiazolidine, NTZ was a new broad spectrum parasiticides,molluscicidal and antimicrobial agent.It has activity against Protozoa,Trematode,Nematode Helminth infection and sensitive enter-bacterium infection. NTZ is one of the first-line drugs for the treatment of Cryptosporidium infection.NTZ is not shown in the Chinese drug market by now,it is the second type of new veterinary drug. Nitazoxanide suspension and tablets as used in this study,according to"veterinary chemical drug tests clinical pharmacokinetics guiding principles"issued by Ministry of Agriculture,Pharmacokinetics of this two formulations were studied in this paper.In this study,the major active metabolite of Nitazoxanide in plasma of Beagle dog was determined by LC-MS\MS. The mass spectrometer was operated in the negative ion detection modeusing multiple reaction monitoring (MRM)scan. The temperature of the Ionspray source was set to 550℃, the ion spray voltage was -4.5kv,Nitrogen was used as the nebulizing gas,curtain gas and auxiliary gas,with values of 35psi,35psi,35psi. The declustering potential 60 V,Nitrogen was used as collision gas at a pressure of 6psi, The protonated molecules of T (m/z 264.0) and Nifuroxazide (m/z 273.9) were fragmented in the collision cells. An welchrom-C18 HPLC column(4.6*250mm,5μm)was used to separate T, The column was set at 30℃.The mobile phase consisted of acetonitrile and ultrapure water(60:40,v/v)at a flow rate of 400μL·min-1.A double acetonitrile precipitation method was developed for plasma purification procedure. A good linear relationship was obtained from 0.02-25μg.mL-1.The LOD and the LOQ were 3.3ng·mL-1and 10ng·mL-1 for Tizoxanide in Beagle dog plasma.The recovery of different concentrations were all above 80%, the Intra-day precision and Inter-day precision were controlled under 5%. The result showed that this method was simple, reliable and sensitive,it can be used in the pharmacokinetic study of Nitazoxanide.In pharmacokinetic experiments, a low, medium and high doses were used. Pharmacokinetic parameters were caculated by 3P97.The result showed that it meeted the first-order rate process of one compartment model.The main pharmacokinetic parameters after giving 33,100,300mg/kg·bw NTZ suspension were as follows: Tmax: 4h of all administration, t1/2:3.32±0.37,2.52±0.29,2.91±0.18h,Cmax: 0.85±0.09,2.80±0.48,10.38±0.21μg.mL-1,AUC: 1.83±0.14,5.21±0.28,15.35±0.42μg.mL-1.h. The main pharmacokinetic parameters after giving 33,100,300mg/kg·bw NTZ tablets were as follows: Tmax: 4h of all administration, t1/2: 2.86±0.26,3.01±0.25,2.83±0.19h , Cmax:0.32±0.02,1.03±0.12,3.11±0.21μg.mL-1, AUC:1.83±0.14,5.21±0.28,15.35±0.42μg.mL-1.h. The above data to accelerate the formulation of nitazoxanide clinical use provides a theoretical basis.
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