Pharmacokinetic profile of lesogaberan (AZD3355) in healthy subjects: a novel GABA(B)-receptor agonist reflux inhibitor

Objective: The aim of this study was to evaluate the pharmacokinetic profile of lesogaberan in healthy subjects after single oral and intravenous administration of ¹⁴C-labeled lesogaberan and non-¹⁴C-labeled lesogaberan.Study Design: This was an open-label, single-center, randomized, two-way crossover, phase I study.Participants: Ten healthy male subjects took part in the study.Intervention: Volunteers were randomized to receive a single dose of either orally dosed (100 mg) or intravenously infused (20 mg) non-¹⁴C-labeled lesogaberan, and then orally (100 mg) or intravenously (20 mg) administered ¹⁴C-labeled lesogaberan in a crossover design. Treatment periods were separated by a washout period of at least 7 days.Main Outcome Measures Analyses of the rate and route of excretion, dose recovery, area under the plasma concentration versus time curve (AUC), AUC to the last quantifiable concentration, maximal plasma concentration (C_max), time to C_max, the apparent elimination half-life, bioavailability, total clearance, renal clearance, fraction of the bioavailable dose excreted unchanged in the urine, cumulative amount of drug excreted unchanged in urine, and the apparent volume of distribution at steady state of lesogaberan.Results: Lesogaberan was rapidly and extensively absorbed from the gastrointestinal tract and C_max was achieved within 1–2 hours of oral dosing. The terminal half-life of lesogaberan was between 11 and 13 hours. Renal clearance accounted for approximately 22% of total body clearance. Based on the recovery of administered radioactivity, approximately 84% of the dose was excreted into the urine either as the parent compound or as water-soluble metabolite(s). There were no safety concerns raised during the study.Conclusion: Orally administered lesogaberan is rapidly absorbed with high bioavailability and the majority of the dose is excreted by the kidneys either as the parent compound or as metabolites. The major elimination pathway for lesogaberan in man is metabolism.     

Toxic effects and excretion in urine of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the rat after a single oral dose

Toxic effects and excretion in urine of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), the potent mutagenic compound in chlorinated drinking water, was evaluated in male Wistar rats by the up-and-down method. MX was dosed by gavage in deionized water at doses between 200 mg/kg and 600 mg/kg, for one animal at a time, and effects were observed for 14 days. Urine was collected in metabolism cages up to 72 h after dosing for chemical analysis of MX in urine. The animals receiving 200 mg/kg did not display clear clinical signs but at higher doses the signs of ill effects included dyspnea, laborious, wheezing and gasping breathing, decreased spontaneous motor activity, ataxia, nostril discharges, catalepsia and cyanosis. In necropsy bronchi contained foamy liquid and the lungs appeared edematous and spongy. The stomach cavity was expanded due to accumulation of fluid and gas and the gastrointestinal tract from stomach to caecum was reddish. Microscopically, the main target organ of toxicity was the gastrointestinal tract (diffuse congestion and necrosis in the mucosa). Signs of toxicity were recorded also in lungs (slight edema) and kidneys (dilated tubules, thin tubular epithelium, brownish tubular and interstitial concretion). The LD₅₀ in 48 h was 230 mg/kg. Only 0.03 – 0.07% of the dose (200 mg/kg or 300 mg/kg) was excreted in urine as intact MX. The results indicate that at high doses MX has a strong local irritating effect in the gastrointestinal tract and it probably increases liquid permeability in lungs. MX may also cause tubular damage in kidneys. Data also indicate that after an oral dose only traces of MX are excreted in urine as intact compound, suggesting that MX is subjected to intense metabolism before excretion, even at lethal doses. Received: 14 December 1993/Accepted: 28 February 1994     

Pharmacokinetics and metabolism of α-[(dimethylamino)methyl]-2-(3-ethyl-5-methyl-4-isoxazolyl)-1H-indole-3-methanol,a hypoglycemic agent,in man

1. The pharmacokinetics and metabolism of α-[(dimethylamino)methyl]-2-(3-ethyl-5-methyl-4-isoxazolyl)-1H-[3-¹⁴C] indole-3-methanol, a new hypoglycemic agent, have been studied in 15 healthy male volunteers who received an oral dose of 50 or 200 mg.

2. The drug was rapidly and almost completely absorbed intact from the gastrointestinal tract.

3. Compared with the 50 mg dose, the 200 mg dose yielded less than proportionally higher blood concentrations of radioactivity and unchanged drug. This phenomenon has been observed previously in the rat and was probably due to an increase in drug distribution volume with increasing dose, since the metabolism and excretion patterns of the drug appeared to be dose-independent.

4. The drug was partially metabolized prior to excretion. Approximately 40% of the dose was recovered intact, almost exclusively in urine. The major metabolic pathway of the drug was by conjugation with glucuronic acid, while oxidation of the indole ring gave rise to a relatively minor metabolite.

5. The recovery of administered radioactivity was virtually complete within the experimental period, with a renal: faecal excretion ratio of ca 80: 20. The elimination half-life of unchanged drug was 25-30h while that of total radioactivity was 33-35 h.     

Disposition of rubratoxin B in the rat

Excretion, tissue concentrations in the kidney and liver, and pharmacokinetic parameters estimated from plasma blood concentrations were determined for rats given a single ip dose of [¹⁴C]rubratoxin B (0.05 mg dissolved in propylene glycol). By 7 days, 80% of the administered radioactivity had been excreted into the urine (41.7%) and feces (38.7%). Urinary excretion was primarily as the parent compound, accounting for 75% of the radioactivity excreted by 7 days. Elimination of radio-activity from the kidneys was monophasic with a half-life of 97.35 hr. Elimination of radioactivity from the liver was biphasic, with a half-life of 13.66 hr for the slow phase. Elimination of rubratoxin B and [¹⁴C]rubratoxin B-derived radioactivity (radioactivity derived from both the parent compound and metabolites) from the plasma was biphasic. The rapid phases of elimination had half-lives of 2.57 and 1.08 hr, and the slow phases had half-lives of 60.80 and 100.46 hr for rubratoxin B and [¹⁴C]rubratoxin B-derived radio-activity respectively. The long plasma half-life of rubratoxin B is suggestive of enterohepatic circulation. The concentration of radioactivity was greatest at 1 hr in the liver and 2 hr in the plasma. Except for the first few hours following injection, the concentration of radioactivity in the liver never exceeded significantly that in the plasma, suggesting a passive absorption process. No glucuronide or sulfate conjugates were detected in the plasma or urine.     

葛根有效成分的代谢研究——Ⅱ.14C-黄豆甙元在大鼠体内的吸收、分布和消除

本文采用纸片液体闪烁计数法研究了¹⁴C-黄豆甙元在大鼠体内的吸收、分布和消除。大鼠口服¹⁴C-黄豆甙元30分钟,血液即可测出放射性,6～8小时达高峰,以后缓慢下降。口服给药吸收不完全,由实验推论约有64.6%放射性可被吸收。静脉注射后,血放射性消失曲线分为快、慢两个时相,其生物半衰期分别为13分钟和42分钟。放射性在肾、肝含量最高,血浆、肺、心次之,肌肉、脾、睾丸、脑较低。静脉注射后,¹⁴C主要自尿排出(24小时可排出剂量的71.2%),自粪排出17.4%。口服后24小时可自尿排出34.3%,自粪排出33.1%。胆汁也是一条重要排泄途径,静脉注射后24小时可自胆汁排出剂量的47.4%;口服后相应时间内排出39.1%。本文所得结果与前文应用化学方法所得结果进行比较,表明自消化道、尿、胆汁所回收的放射性主要是黄豆甙元的代谢产物,说明该药在体内的代谢很旺盛。     

Pharmacokinetic and metabolic studies of vinpocetine on dogs. I. Pharmacokinetics

The pharmacokinetics of tritiated vinpocetine has been studied on dogs. The drug, when administered orally, was readily absorbed from the gastrointestinal tract (T1/2 0.3 h) and underwent similarly fast distribution (T1/2 0.8 h) in the organism. The mean value of the elimination half-life was 8.2 h. Approx. 75% of the administered radioactivity was excreted with urine and feces within 72 h. The pharmacokinetics of the intravenously administered, labelled compound showed that a similarly rapid distribution but a somewhat slower elimination took place. Fecal and urinary excretion of radioactivity applied amounted to about 82%. Investigation of the distribution of radioactivity between plasma and blood cells revealed that the radioactivity content did not bind to the cellular fraction of the blood. Pharmacokinetic studies of the same design in the literature allowed us to make some comparison between dogs, rats and humans in respect to the kinetic behavior of labelled vinpocetine.     

Metabolism and disposition of the flame retardant tris(2,3-dibromopropyl)phosphate in the rat

The metabolism and disposition of the flame retardant, tris(2,3-dibromopropyl)phosphate (Tris-BP), were studied after po and iv administration of the 14C-labeled compound to the male rat. Tris-BP was readily absorbed from the gastrointestinal tract and rapidly distributed throughout the body. The distribution and excretion of Tris-BP derived radioactivity were similar after either po or iv administration. The only effects of route of administration on tissue distribution were slightly higher concentrations in liver after po administration and in lung after iv administration. The initial elimination of Tris-BP derived radioactivity in urine, feces, and as CO2 accounted for approximately 50% of the dose in 24 hr. An analysis of Tris-BP derived radioactivity remaining in the tissues one day after administration indicated that most of the radioactivity in all tissues was in the form of various metabolites rather than the parent compound. The terminal clearance of Tris-BP derived radioactivity from most of the tissues studied was best described by a single component exponential decay with a half-life of approximately 2.5 days. Clearance from liver and kidney was somewhat slower having a half-life of approximately 3.8 days. Approximately 33% of the radioactivity excreted in urine and approximately 50% of the radioactivity excreted in bile were identified by cochromatography with synthesized standards on high performance liquid chromatography (HPLC). Six metabolites and a trace of the parent compound were identified in urine and bile by this method. The six metabolites products of dealkylation and dehydrobromination of the parent compound. The metabolites of Tris-BP isolated from urine and bile were also formed in vitro by NADPH-dependent microsomal enzymes from rat liver. The soluble enzymes from liver metabolized Tris-BP to at least three unidentified polar metabolites.     

Pharmacokinetics and metabolism of alpha-[(dimethylamino)methyl]-2- (3-ethyl-5-methyl-4-isoxazolyl)-1H-indole-3-methanol, a hypoglycemic agent, in man

1. The pharmacokinetics and metabolism of alpha-[(dimethylamino)methyl]-2-(3-ethyl-5-methyl-4-isoxazolyl) -1H-[3-14C]indole-3-methanol, a new hypoglycemic agent, have been studied in 15 healthy male volunteers who received an oral dose of 50 or 200 mg. 2. The drug was rapidly and almost completely absorbed intact from the gastrointestinal tract. 3. Compared with the 50 mg dose, the 200 mg dose yielded less than proportionally higher blood concentrations of radioactivity and unchanged drug. This phenomenon has been observed previously in the rat and was probably due to an increase in drug distribution volume with increasing dose, since the metabolism and excretion patterns of the drug appeared to be dose-independent. 4. The drug was partially metabolized prior to excretion. Approximately 40% of the dose was recovered intact, almost exclusively in urine. The major metabolic pathway of the drug was by conjugation with glucuronic acid, while oxidation of the indole ring gave rise to a relatively minor metabolite. 5. The recovery of administered radioactivity was virtually complete within the experimental period, with a renal:faecal excretion ratio of ca 80:20. The elimination half-life of unchanged drug was 25-30 h while that of total radioactivity was 33-35 h.     

14C-棉酚在四种动物体内吸收、分布和排泄的比较研究

本文比较研究了¹⁴C-棉酚在小鼠、大鼠、犬和猴体内的吸收、分布和排泄过程。小鼠和大鼠于单次口服¹⁴C-棉酚后6～9小时,血内放射性达高峰,生物半衰期分别为31和16.5小时。口服¹⁴C-棉酚48小时后,以胃肠道内容物及肝、肾内放射性最高。睾丸内放射性大鼠比小鼠要高。进入体内¹⁴C-棉酚,放射性排出主要通过粪便,少部分从尿排出。以犬和猴(各1只)进行比较研究,也获得类似结果。它们睾丸内放射性均比大鼠低。与其它三种动物比较,犬心脏内放射性最高,猴体内放射性从粪便中排出最快。本文结果提示棉酚对不同动物的抗生育作用与毒性作用之间的差异,可能与它在相应脏器内的分布、蓄积及排泄速度的不同有关。     

Pharmacokinetic studies on the selectiveβ 1-receptor antagonist metoprolol in man

The pharmacokinetics of ³H-metoprolol, a new selective ₁-receptor antagonist, have been studied in healthy volunteers by following the plasma concentrations and the urinary excretion of the unchanged compound and its total radioactive metabolites after oral and intravenous administration. The compound was rapidly and completely absorbed after oral administration, and about 40% of the dose reached the systemic circulation. The estimated half-life of the absorption process was 10 min. Metoprolol was extensively distributed to extravascular tissues, with the half-life of the distribution phase close to 12 min. About 95% of the dose was excreted in the urine within 72 hr, mainly in metabolized form. The elimination halflife of the compound was close to 3 hr as was also the half-life of the total metabolites after oral administration. After intravenous administration, the elimination half-life of the metabolites was raised to 5 hr, indicating that the route of administra tion might influence the metabolic pathways of the parent compound.     

高三尖杉酯碱在大鼠及小鼠的代谢

本文报告³H-高三尖杉酯碱在正常大鼠、小鼠和荷瘤小鼠体内的吸收、分布和排泄。给大鼠静注后,t_1/2(α)和(β)分别为2.1和53.7分钟。静注后15分钟,以骨髓、肾和肝的放射性最高。荷瘤小鼠体内的放射性分布情况与正常大鼠的趋势相仿。静注后24小时,自大鼠尿排泄剂量的42.2%,在粪中排出6.3%,其中原形药放射性占剂量的15.9%。静注后48小时,自胆汁排泄剂量的57.7%,其中原形药放射性占剂量的20.2%。该碱经肌注也可被迅速吸收入血。     

The Metabolic Fate of the Coronary Dilator 4-(3,4,5-Trimethoxycinnamoyl)-1-(N-Isopropylcarbamoylmethyl)- Piperazine in the Rat,Dog and Man

1. An oral dose of the coronary dilator 4-(3,4,5-trimethoxycinnamoyl)-1- (N-isopropylcarbamoylmethyl)-piperazine was readily absorbed and more than 75% of the dose was excreted within 24 h by the rat, dog and man. In 4 days, rat, dog and man excreted in the urine and faeces respectively 32.5 and 62.3%, 43.9 and 49.1%, and 57.8 and 43.3%. Faecal radioactivity was mainly excreted via the bile.

2. Plasma concentrations of radioactivity reached a maximum within 1 h in rats and dogs and within 2 h in man. For several h, more than 50% of the radioactivity circulating in the plasma of rats and more than 80% in man was due to unchanged drug.

3. Sequential whole-body autoradiography of the rat indicated that much of the radioactivity was distributed in the liver, kidneys and gastrointestinal tract and that there was significant uptake into the heart and lungs.

4. Although similar metabolites were excreted by the rat, dog and man, the relative proportions differed. 11.7, 2.3 and 28.8% respectively of the unchanged drug were excreted in the urine and 13.1, 19.5 and 10.4% respectively of the principal metabolite a glucuronide whose exact structure was not determined. Other metabolites included 4-(3,4,5-trimethoxycinnamoyl)-1-carbamoylmethyl piperazine and N-(3,4,5-trimethoxycinnamoyl)-piperazine.     

Pharmacokinetics of [6]-shogaol,a pungent ingredient of <Emphasis Type="Italic">Zingiber officinale</Emphasis> Roscoe (Part I)

To investigate the pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe, the pharmacokinetic parameters were determined by using ¹⁴C-[6]-shogaol (labeled compound) and [6]-shogaol (non-labeled compound). When the labeled compound was orally administered to rats, the maximum plasma concentration (C _max) and the area under the curve (AUC) of plasma radioactivity concentration increased in a dose-dependent manner. When the labeled compound was orally administered at a dose of 10 mg/kg, 20.0 ± 1.8% of the radioactivity administered was excreted into urine, 64.0 ± 12.9% into feces, and 0.2 ± 0.1% into breath. Thus, more of the radioactivity was excreted into feces than into urine, and almost no radioactivity was excreted into breath. Furthermore, when the labeled compound was orally administered at a dose of 10 mg/kg, cumulative biliary radioactivity excretion over 48 h was 78.5 ± 4.5% of the radioactivity administered, and cumulative urinary radioactivity excretion over 48 h was 11.8 ± 2.7%, showing that about 90% of the dose administered orally was absorbed from the digestive tract and most of the fecal excretion was via biliary excretion. On the other hand, when the non-labeled compound [6]-shogaol was orally administered, the plasma concentration and biliary excretion of the unchanged form were extremely low. When these results are combined with those obtained with the labeled compound, it would suggest that [6]-shogaol is mostly metabolized in the body and excreted as metabolites.     

Paraquat disposition in rats, guinea pigs and monkeys

LD50 doses of ¹⁴C-labeled paraquat were administered to rats, guinea pigs and monkeys by gavage, and radioactivity was determined in excreta and tissues. Rat urine was analyzed for paraquat metabolites by thin-layer chromatography. [¹⁴C]Paraquat was absorbed from the gastrointestinal tract and reached highest serum values 0.5–1 hr after administration. Disappearance of [¹⁴C]paraquat from serum was characterized by a rapid initial decline followed by a prolonged slow decline. Tissue paraquat values were higher than serum values in rats and guinea pigs. Relative to other tissues, paraquat accumulated transiently in the lung and reached peak concentration 32 hr after administration. In rats a major portion of administered paraquat was not absorbed from the gastrointestinal tract. At 32 hr after paraquat, 52% of the administered dose remained in the gastrointestinal tract and 17 and 14% of the administered dose was excreted in the feces and urine, respectively. No radioactivity was recovered in expired air or flatus. Excretion of paraquat in urine and feces was prolonged in all species. In monkeys paraquat was measured in urine and feces 21 days after administration. Chromatography of urine from [¹⁴C]paraquat-treated rats revealed no metabolites. The primary pathologic changes induced by paraquat in the lung may be related to the transient uptake of the chemical by that organ.     

Biodistribution and Excretion of Radiolabeled 40 kDa Polyethylene Glycol Following Intravenous Administration in Mice

The pharmacokinetics, excretion, and tissue distribution of [¹⁴C]-labeled polyethylene glycol–alanine (PEG–Ala) were determined after slow bolus administration into the femoral vein of male CD-1 mice. The pharmacokinetics of PEG–Ala in blood and plasma revealed a biphasic elimination with a terminal half-life of 20 h. Eighty-five percent of the excreted material was voided in the urine and the remaining amount was detected in the feces. PEG–Ala-derived radioactivity was widely distributed with detectable levels of radioactivity observed in all tissues examined. The highest concentration was observed in the kidneys followed by lungs, heart, and liver. Six hours after administration, PEG–Ala levels were significantly reduced in all tissues. Despite a slow prolonged decrease, radioactivity was still detectable after 28 days. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2362–2370, 2013     

奥拉西坦在大鼠和小鼠的药代动力学研究

目的： 研究奥拉西坦(ORC)在大鼠和小鼠的药代动力学。方法： 采用HPLC法测定生物样品中ORC浓度, 在大鼠和小鼠进行其药代动力学、吸收、分布、排泄试验。结果： 大鼠灌胃给ORC 100,200和400 mg.kg^-1后表明, 本品po吸收速率快,达峰时间短,药物自血清消除较快。小鼠1次ig给药100 mg.kg^-1后,80%以上药物在给药后3 h内由消化道消失;药物吸收后能分布到各种组织脏器, 给药后36 h累计尿排泄原形药物量约为药物剂量的80%; 蛋白结合率低,平均结合率为10.5%。结论： 奥拉西坦是一吸收快、消除快、主要以原形药物由尿排泄、蛋白结合率低的药物。     

A dose-dependent pharmacokinetic study on caffeic acid in rabbits after intravenous administration

The dose-dependent pharmacokinetics of caffeic acid (CA) were studied in rabbits. Three different doses (5, 10, and 25 mg kg⁻¹) were administered intravenously to six rabbits each. The concentration–time profiles for CA could be fitted by a two-compartment model for each dose. The results showed that total-body clearance and elimination rate constant from the central compartment (k₁₀) after a 5 mg kg⁻¹ dose were greater than those after the other two doses. Furthermore, the terminal elimination half-life (β half-life) and mean residence time (MRT) after a 5 mg kg⁻¹ dose were less than after the other doses. The AUC value increased linearly with dose within the range of 10–25 mg kg⁻¹. Most of the unchanged caffeic acid was excreted in the urine within 2 h. The percentage of unchanged caffeic acid excreted in the urine was 63·4, 60·0, and 55·4% after doses of 5, 10, and 25 mg kg⁻¹, respectively, which was not significantly different. However, significant differences in the renal clearances and renal excretion rate constants were observed with a 5 mg kg⁻¹ dose compared to the other doses. On the other hand, nonrenal clearances and nonrenal excretion rate constants showed no dose-related differences. The differences observed in total-body clearance, k₁₀, β half-life, and MRT between a 5 mg kg⁻¹ dose and the other doses can be explained on the basis of the differences in renal clearance and renal excretion rate constants. ©1997 John Wiley & Sons, Ltd.     

The metabolic disposition of (S)-2-(3-tert-butylamino-2-hydroxypropoxy)-3-cyanopyridine in rats, dogs, and humans

Studies of the metabolic disposition of (S)-2-(3-tert-butylamino-2-hydroxypropoxy)-3-[14C]cyanopyridine (I) have been performed in humans, dogs, and spontaneously hypertensive rats. After an iv injection of I (5 mg/kg), a substantial fraction of the radioactivity was excreted in the feces of rats (32%) and dogs (31%). After oral administration of I (5 mg/kg) the urinary recoveries of radioactivity for rat and dog were 19% and 53%, respectively, and represented a minimum value for absorption because of biliary excretion of radioactivity. In man, bililary excretion of I appeared to be of minor significance because four male subjects, after receiving 6 mg of I p.o., excreted 76% and 9% of the dose of radioactivity in the urine and feces, respectively. Unchanged I represented 58% of the radioactivity excreted in human urine. The half-life for renal elimination of I was determined to be 4.0 +/- 0.9 /hr. In contrast, unchanged I represented 7% and 1% of excreted radioactivity in rat and dog urine, respectively. A metabolite of I common to man, dog, and rat was identified as 5-hydroxy-I, which represented approximately 5% of the excreted radioactivity in all species. Minor metabolites of I in which the pyridine nucleus had undergone additional hydroxylation were present in dog urine along with an oxyacetic acid metabolite, also bearing a hydroxylated pyridine nucleus.     

Absorption,Excretion and Urinary Metabolic Pattern of 3H-Albuterol Aerosol in Man

1. After inhalation of doses of ³H-albuterol (84 and 220 μg) by humans, plasma radioactivity reached a max. after 2 and 4?h, respectively.

2. About 72% of the inhaled dose was excreted within 24?h in urine and a similar urinary excretion pattern was obtained with both dosages. From the excretion pattern of the unchanged drug in urine a half-life of 3.8?h and an elimination constant of 0.18 h^?1 for albuterol were calc.

3. Approx. 28% dose was excreted as unchanged albuterol, 40% as a major urinary metabolite and 4% as a minor metabolite. The major metabolite could be converted to an albuterol-like compound by acid hydrolysis but not enzymically (Glusulase).

4. These results show that albuterol as an aerosol is readily absorbed, and is excreted mainly in the urine as the free drug and at least two metabolites.     

3H羟基斑蝥胺的药物代谢动力学研究

将氚标记的羟基斑蝥胺在大鼠体内研究了药物代谢动力学。所得血药浓度-时间数据依一定程序在709电子计算机上拟合曲线,并计算有关参数。结果表明,静脉注射后符合二房室开放型模型,其药代动力学参数为:t1/2α0.067hr,t1/2β2.208hr,V_d(面积)1.237l/kg,V₁0.264l/kg,K_el1.470 hr^-1,清除率0.388l/hr/kg。灌胃后可以单室开放型模型描述,其药代动力学参数为:K_α2.990hr^-1,K_el0.257hr^-1,V_d1.603l/kg,t1/22.693hr,t_max0.90hr,C_max0.745μg/ml,F94.15%。尚将本药以静脉和灌胃两种途径给药后直接观察在大鼠体内的组织分布和在尿粪胆汁中的排泄,结果表明本药分布广,主要经肾排泄,且排泄较快,与药代动力学分析结果相一致。