背景:肥胖可能改变几种药物的组织分布和清除,尤其是亲脂性的.伊曲康唑,一种亲脂性药物,最近已在用于治疗皮肤癣菌病的超生物可利用制剂(SB-ITZ)中引入。缺乏关于SB-ITZ在肥胖症中的最佳剂量的证据。目前的实验研究计划分析肥胖和非肥胖大鼠中不同剂量的SB-ITZ的组织浓度。材料和方法将36只Wistar白化病大鼠分为肥胖和非肥胖大鼠。Further,将这两类大鼠分为三个给药组。第1组早上接受SB-ITZ13mg,每日一次,第2组早上接受SB-ITZ13毫克,晚上接受6.5毫克,而第3组大鼠每天两次接受SB-ITZ13mg,orally.SB-ITZ在皮肤中的浓度,血清,在第7,14,21和28天评估每组的脂肪组织。在第28天进行肥胖和非肥胖大鼠中各种组织中SB-ITZ浓度的比较以及三种给药方案中组织浓度的组间比较,并表示为平均值±SD.36只Wistar大鼠被平均分为肥胖和非肥胖大鼠。结果在第28天,在第1、2和3组中,SB-ITZ的皮肤浓度分别为5.36±1.1、8.9±1.7和10.13±1.7µg/g,在非肥胖大鼠中,与相应给药组的肥胖大鼠的皮肤浓度(分别为2.72±0.6、4.2±0.7和4.66±0.5µg/g)相比,差异有统计学意义(p<0.05)。与第1组相比,第2组和第3组的SB-ITZ的皮肤浓度在统计学上是显著的。尽管如此,在非肥胖和肥胖大鼠中,第2组和第3组之间无统计学差异.在非肥胖和肥胖大鼠的所有3种给药方案中,SB-ITZ的脂肪组织浓度是相当的。但是在组间比较中,观察到第2组和第3组与第1组的统计学差异(p<0.05)。增加SB-ITZ的剂量增加血清浓度。在非肥胖大鼠中,在第2组(74.33±6.6ng/ml)和第1组(52.5±9.9ng/ml)之间观察到统计学上的显着差异;p<0.01,第3组(81.33±6.8ng/ml)与第1组之间也存在统计学上的显着差异;p<0.01。在肥胖大鼠中,第3组的浓度明显高于其他两组(第3组;72±5.3,第2组;60.5±4.3,第1组;45±7ng/ml;p<0.01)。结论总体来说,皮肤,脂肪组织,与所有三个给药组的肥胖大鼠相比,非肥胖大鼠的SB-ITZ血清浓度更高。此外,在非肥胖和肥胖大鼠中,所有组的皮肤和脂肪组织浓度均按比例高于血清.尽管非肥胖大鼠的皮肤浓度明显高于肥胖大鼠,肥胖大鼠的皮肤浓度在最小抑制浓度(MIC)范围内,证明所有给药方案的疗效。
Background Obesity may alter tissue distribution and clearance of several drugs, especially lipophilic ones. Itraconazole, a lipophilic drug, has been recently introduced in a super-bioavailable formulation (SB-ITZ) for the treatment of dermatophytosis. Evidence regarding optimal dosing of SB-ITZ in obesity is lacking. A current experimental study was planned to analyze tissue concentrations of SB-ITZ at different doses in obese and non-obese rats. Materials and methods Thirty-six Wistar albino rats of either sex were divided into obese and non-obese rats equally. Further, rats in both categories were divided into three dosing groups. Group 1 received SB-ITZ 13 mg once daily in the morning, group 2 received SB-ITZ 13 mg in the morning and 6.5 mg in the evening, while Group 3 rats received SB-ITZ 13 mg twice daily, orally. Concentrations of SB-ITZ in the skin, serum, and fatty tissue were assessed in each group on days 7, 14, 21, and 28. Comparison of SB-ITZ concentrations in various tissues in obese and non-obese rats and inter-group comparison of tissue concentrations across the three dosing regimens was done at day 28 and expressed as Mean ± SD.36 Wistar rats were divided into obese and non-obese rats equally. Results At day 28, skin concentrations of SB-ITZ were 5.36±1.1, 8.9±1.7 and 10.13±1.7 µg/g in Groups 1, 2, and 3, respectively, in non-obese rats, which was statistically significant (p<0.05) than skin concentration of obese rats (2.72±0.6, 4.2±0.7 and 4.66±0.5 µg/g) for the corresponding dosing groups respectively. Skin concentration of SB-ITZ was statistically significant for Groups 2 and 3 as compared to Group 1. Still, no statistically significant difference was noted between Groups 2 and 3 in non-obese and obese rats. Fatty tissue concentration of SB-ITZ was comparable in all 3 dosing regimens in non-obese and obese rats. But on the intergroup comparison, a statistically significant difference was observed for Groups 2 and 3 against Group 1 (p<0.05). Increasing the dose of SB-ITZ increased serum concentration. In non-obese rats, a statistically significant difference was noted between Group 2 (74.33±6.6 ng/ml) and Group 1 (52.5±9.9 ng/ml); p<0.01 and also in Group 3 (81.33±6.8 ng/ml) against Group 1; p<0.01. Group 3 achieved significantly higher concentration than the other two groups in obese rats (Group 3; 72±5.3, Group 2; 60.5±4.3, and Group 1; 45±7 ng/ml; p<0.01). Conclusion Overall, skin, fatty tissue, and serum concentrations of SB-ITZ were higher in non-obese rats compared to obese rats in all three dosing groups. Moreover, skin and fatty tissue concentrations were proportionately higher than serum in all the groups in non-obese and obese rats. Though the skin concentration of non-obese rats was significantly higher than obese rats, skin concentration in obese rats was within the minimum inhibitory concentration (MIC) range, demonstrating the efficacy of all dosing regimens.