Gao X, Buffington C A, Au J L
College of Pharmacy, Ohio State University, Columbus.
J Pharmacol Exp Ther. 1994 Nov;271(2):818-23.
Our laboratory reported previously the in vivo absorption of salicylate and antipyrine from the urinary bladder of healthy rats. The present study extends these findings to examine the effect of interstitial cystitis on bladder permeability to drugs by comparing the bladder absorption of salicylate in healthy cats and cats with feline interstitial cystitis (FIC). Interstitial cystitis is a lower urinary tract disease and may involve inflammation of the bladder. A 25-mg/kg dose of sodium salicylate was instilled into the bladder and a 6-micrograms/kg i.v. dose of [14C]salicylic acid was administered concomitantly to determine systemic clearance in individual animals. In healthy and FIC cats, the clearance was 0.3 and 0.1 ml.min-1.kg-1, and the bioavailability of the intravesical dose was about 1 and 9%, respectively. The apparent bladder absorption rate constant and the peak plasma concentration in FIC cats were 7 to 8 times that in healthy cats. These data indicate a significantly higher bladder permeability to salicylate due to interstitial cystitis. In order to elucidate the cause of the lower clearance in FIC cats, a second study compared the disposition of a 2-mg/kg i.v. dose of salicylate in healthy and FIC cats. It was found that the lower salicylate clearance in FIC cats was due in part to a decreased metabolism in the disease state and also involved slower drug elimination at the higher plasma concentrations secondary to the more extensive absorption of the intravesical dose.(ABSTRACT TRUNCATED AT 250 WORDS)
我们实验室之前报道过健康大鼠膀胱对水杨酸盐和安替比林的体内吸收情况。本研究扩展了这些发现,通过比较健康猫和患有猫间质性膀胱炎(FIC)的猫对水杨酸盐的膀胱吸收情况,来研究间质性膀胱炎对膀胱药物通透性的影响。间质性膀胱炎是一种下尿路疾病,可能涉及膀胱炎症。将25mg/kg剂量的水杨酸钠注入膀胱,并同时静脉注射6μg/kg剂量的[14C]水杨酸,以确定个体动物的全身清除率。在健康猫和患有FIC的猫中,清除率分别为0.3和0.1ml·min-1·kg-1,膀胱内给药的生物利用度分别约为1%和9%。患有FIC的猫的表观膀胱吸收速率常数和血浆峰值浓度是健康猫的7至8倍。这些数据表明,由于间质性膀胱炎,膀胱对水杨酸盐的通透性显著更高。为了阐明患有FIC的猫清除率较低的原因,第二项研究比较了2mg/kg静脉注射剂量的水杨酸盐在健康猫和患有FIC的猫体内的处置情况。结果发现,患有FIC的猫水杨酸盐清除率较低部分是由于疾病状态下代谢降低,还涉及由于膀胱内给药吸收更广泛导致血浆浓度较高时药物消除较慢。(摘要截短至250字)