Pharmacokinetics of α-dihydroergocriptine in rats after single intravenous and single and repeated oral administrations

The pharmacokinetics of α-dihydroergocriptine methane sulphonate in rats were investigated using an HPLC method for the detection of unchanged α-dihydroergocriptine (DHEK) in plasma, organs (kidneys, heart, lungs, spleen, liver, and brain), and urine. The plasma profile of DHEK obtained after intravenous administration at a dose of 5 mg kg^?1 (as base) of DHEK methane sulphonate showed a three compartment pharmacokinetic model with an elimination half-life of 6.78 h. The kinetics of DHEK after a single oral administration at a dose of 20 mg kg^?1 (as base) showed two peaks: the second peak, at about 6 h, was probably due to an enterohepatic cycle. The disposition of DHEK consisted of an absorption half-life of 0.02 h, a distribution half-life of 2.15 h and an elimination half-life of 5.83 h. The pharmacokinetics of DHEK, after repeated oral administrations at the same dose, were similar to those after a single oral administration. The absolute bioavailability was 4.14% after a single oral administration and 3.95% after repeated oral administrations. The analysis of the organs showed that DHEK was rapidly absorbed and distributed in all tissues, mostly in lungs, kidneys, and liver, but it is interesting to observe that it also reached the brain. After repeated oral administrations plasma and tissue concentrations were similar to those obtained after a single administration; therefore it is possible to exclude the onset of autoinduction or accumulation phenomena of DHEK in rats' organs. Urinary excretion of the unchanged drug was low (0.38% of the administered dose in the intravenous route and 0.04% in the oral route), being in agreement with a low oral bioavailability and a rapid and extensive metabolism (first-pass effect).     

Pharmacokinetics of huperzine A in dogs following single intravenous and oral administrations

The pharmacokinetics of huperzine A in dogs after single intravenous and oral administrations was investigated. Concentrations of huperzine A were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated by non-compartmental methods. After single intravenous administration, the Cmax, T1/2, AUC0-t, AUC0-infinity, CL, Vd and Vss were 5.55 +/- 1.61 microg/L, 5.02 +/- 0.31 h, 16.04 +/- 5.24, 16.49 +/- 5.29 microgh/L, 0.66 +/- 0.19 L/h/kg, 4.76 +/- 1.46, and 3.93 +/- 1.54 L/kg, respectively. After single oral administration, the Cmax, Tmax, T1/2, AUC0-t, AUC0-infinity and oral bioavailability were 2.60 +/- 0.60 microg/L, 1.25 +/- 0.50 h, 5.71 +/- 2.25 h, 12.90 +/- 3.19, 13.78 +/- 3.24 microgh/L, and 94.4 +/- 36.5%, respectively. In conclusion, huperzine A had a rapid and nearly complete oral absorption and was extensively distributed into tissues after drug administration in dogs.     

Pharmacokinetics of fostedil, a new calcium antagonist, in beagle dogs following oral and intravenous administration

Twelve adult beagle dogs received both an oral and intravenous dose (12 mg/kg) of fostedil in a cross-over design. The plasma levels and urinary excretion of intact fostedil were measured, and the pharmacokinetic parameters of the drug were defined. The results indicate that fostedil was at least 68% bioavailable after an oral dose given as a suspension or solution. The terminal half-life was about 7-8 h. The in vitro protein binding, at concentrations of 0.1-100 micrograms/mL, ranged from 95 to 97%. The binding was not concentration dependent, and saturation of the binding sites was not apparent at concentrations up to 100 micrograms/mL. Excretion of unchanged drug from the kidneys accounted for only a small percentage of drug clearance.     

Pharmacokinetics and metabolism of neferine in rats after a single oral administration

The present study utilized HPLC and LC-MS approaches to investigate the pharmacokinetics and metabolism of neferine (a bisbenzylisoquinoline alkaloid). The plasma concentration-time curves of neferine (10, 20 and 50 mg/kg, i.g.) showed double absorption peaks with the first peak at 10 min and the second peak at 1 h. The t(1/2) (beta) was 15.6 h, 22.9 h and 35.5 h, for each of these doses, respectively. Neferine distributed rapidly into different organ systems, with the highest concentrations found in the liver, followed by the lung, kidney and heart at doses of 10 or 20 mg/kg. At 50 mg/kg dose, concentrations of the kidney and lung were higher than those of others. Moreover, this compound was mainly metabolized in the liver and converted partially by CYP2D6 to liensinine, isoliensinine, desmethyl-liensinine and desmethyl-isoliensinine.     

Pharmacokinetics of a new reversible proton pump inhibitor,YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats

The pharmacokinetics of YH1885 were evaluated after intravenous (iv) and oral administrations of the drug to rats and dogs. The reason for the low extent of bioavailability (F) of YH1885 after oral administration of the drug to rats and the absorption of the drug from various rat gastrointestinal (GI) segments were also investigated. After iv administration of YH1885, 5–20 mg kg⁻¹, to rats, the pharmacokinetic parameters of YH1885 seem to be independent of the drug at the dose ranges studied. After oral administration of YH1885, 50–200 mg kg⁻¹, to rats, the area under the plasma concentration–time curve from time zero to 12 or 24 h (AUC_{0–12 h} or AUC_{0–24 h}) was proportional to the oral dose of the drug, 50–100 mg kg⁻¹, however, the AUC_{0–24 h} value at 200 mg kg⁻¹ increased with less proportion to the dose increase (324, 689, and 815 μg · min mL⁻¹ for 50, 100, and 200 mg kg⁻¹, respectively) due to the poor water solubility of the drug. This was proved by the considerable increase in the percentages of the oral dose remaining in the entire GI tract as unchanged YH1885 at 24 h (11.8, 15.3, and 42.8% for 50, 100, and 200 mg kg⁻¹, respectively). The F value after oral administration of YH1885 to rats was relatively low; the value was approximately 40% at the oral dose of 50 and 100 mg kg⁻¹. The reason for the low F in rats was investigated. The liver showed the highest metabolic activity for YH1885 based on an in vitro rat tissue homogenate study; hence, the liver first-pass effect was estimated. The value of AUC after intraportal administration of the drug, 5 mg kg⁻¹, was approximately 70% (116 versus 163 μg · min mL⁻¹) of that after iv administration of the drug, 5 mg kg⁻¹, to rats; the liver first-pass effect of YH1885 in rats was estimated to be approximately 30%. The total body clearance of YH1885 after iv administration of the drug, 5–20 mg kg⁻¹, to rats were considerably lower than the cardiac output of rats, indicating that the lung and/or heart first-pass effect of YH1885 could be negligible in rats. After oral administration of YH1885, 50 and 100 mg kg⁻¹, to rats, the F value was approximately 40%, and approximately 15% of the oral dose was recovered from the entire GI tract as unchanged YH1885 at 24 h, and 30% of the oral dose disappeared with the liver first-pass effect. Therefore, the remainder, approximately 15% of the oral dose, could have disappeared with the small intestine first-pass effect and/or degradation of the drug in the GI tract. YH1885 was absorbed from ileum, duodenum, and jejunum of rat, however, YH1885 was under the detection limit in plasma when the drug was instilled into the rat stomach and large intestine. After iv administration of YH1885, 5–20 mg kg⁻¹, to dogs, the pharmacokinetic parameters of YH1885 also seemed to be independent of the drug at the dose ranges studied. However, after oral administration of YH1885, 0.5 and 2 g per whole body weight, to dogs, the AUC_{0–10 h} values were not significantly different (96.8 versus 98.2 μg · min mL⁻¹) and this could be due to the poor water-solubility of the drug. YH1885 was not detected in the urine after both iv and oral administration of the drug to both rats and dogs. Copyright © 1998 John Wiley & Sons, Ltd.     

Design and evaluation of oral nanoemulsion drug delivery system of mebudipine

Abstract

A nanoemulsion drug delivery system was developed to increase the oral bioavailability of mebudipine as a calcium channel blocker with very low bioavailability profile. The impact of nano-formulation on the pharmacokinetic parameters of mebudipine in rats was investigated. Nanoemulsion formulations containing ethyl oleate, Tween 80, Span 80, polyethylene glycol 400, ethanol and deionized water were prepared using probe sonicator. The optimum formulation was evaluated for physicochemical properties, such as particle size, morphology and stability. The particle size of optimum formulation was 22.8?±?4.0?nm. Based on the results of this study, the relative bioavailability of mebudipine nanoemulsion was enhanced by about 2.6-, 2.0- and 1.9-fold, respectively, compared with suspension, ethyl oleate solution and micellar solution. In conclusion, nanoemulsion is an interesting option for the delivery of poorly water soluble molecules, such as mebudipine.     

Pharmacokinetics of pantoprazole following single intravenous and oral administration to healthy male subjects

Summary The plasma pharmacokinetics of pantoprazole have been investigated following single intravenous infusion and single oral administration at a dose of 40 mg to 12 healthy male subjects in a randomised cross-over study. Both treatments were generally well tolerated and no relevant compound-related adverse events were noted. The plasma pharmacokinetics of pantoprazole following intravenous infusion in this group of subjects were characterised by a total plasma clearance of 0.13 l·h⁻¹·kg⁻¹ and apparent terminal elimination half-life 1.9 h. The apparent volume of distribution estimated at steady state (0.171·kg⁻¹) was compatible with the localization of a major fraction of the compound in extracellular water. Following oral administration as an enteric-coated tablet formulation, a variable onset of absorption was followed by rapid attainment of maximum plasma concentrations of pantoprazole. Pantoprazole was well absorbed following oral administration; the absolute systemic bioavailability of the compound was estimated as 77% (95% CI, 67 to 89%).     

单次静脉美罗培南在健康人体的药代动力学

目的 研究单剂量美罗培南静脉制剂药代动力学,为临床提供合理给药方案。方法 中国健康受试者10名随机分组交叉给药,30 min内静脉点滴美罗培南500,1 000mg,分别在给药前,给药后0.25,0.5,0.75,1,1.5,2,3,4,5,6,8 h取血,并于0~2,2-6,6～12,12—24 h留取尿样本,用高效液相色谱法测定美罗培南血药浓度及尿药浓度。结果 血药浓度数据经3P97程序分析血药浓度-时间曲线为二室模型,静脉点滴500,1 000 mg主要药代动力学参数Cmax分别为23.08±4.00,48.19±9.78 mg·L-1,AUC分别为27.47±3.80,55.56±6.72 mg·h·L-1,,tl/2B分别为1.08±0.19,1.15±0.15 h,CL分别为18.91±2.48,18.68±2.32L·h-1,Vd分别为13.48±2.94,13.93±2.40L。12 h原形药物在尿中累积排泄百分率分别为(60.11±5.20)％与(61.23±9.81)％。结论 美罗培南单次给药在中国健康人体耐受良好,药物主要经肾脏排泄。     

布洛芬精氨酸注射及口服给药在大鼠体内的立体选择性药代动力学

利用手性高效液相色谱法研究大鼠注射及口服布洛芬精氨酸之后布洛芬对映体的药代动力学。布洛芬精氨酸注射及口服给药后, 布洛芬对映体的药代动力学呈现立体选择性, 且口服给药后立体选择性程度更高。与系统前转化相比, R-布洛芬至S-布洛芬的系统转化在口服给药后立体选择性药代动力学中起更重要的作用。布洛芬精氨酸口服给药后, 优势对映体S-布洛芬迅速吸收, S-布洛芬与R-布洛芬的绝对生物利用度分别为100% 和80%。基于研究发现的S-布洛芬体内系统性暴露, 可以推断布洛芬精氨酸注射及口服给药后的药理作用相似, 仅在作用的起始阶段存在差异。     

Bioavailability and pharmacokinetics of alantolactone from Inula helenium in rats following intravenous and oral administrations

Alantolactone, as the principal constituent of Inula Helenium L, has been shown various pharmacologic activities, such as anti-inflammatory and deworming. In the present study, we developed a high performance liquid chromatography (HPLC) method for the determination of alantolactone in rat plasma, and pharmacokinetics of alantolactone was investigated after intravenous and oral administrations to Wistar rats. Separation was achieved on C₁₈ column (4.6 mm×250 mm, 5.0 μm) using a mobile phase consisting of methanol–water (70:30, v/v) at a flow rate of 1.0 mL/min. The wavelength of the ultraviolet detector was set at 239 nm. The excellent linearity was found over a concentration range of 0.08–10 μg/mL (R² = 0.9998).The intra- and inter-day precisions were good, and the RSD was lower than 2.27%. The mean absolute recovery of alantolactone in plasma ranged from 88.09% to 95.57%. After intravenous administration, alantolactone showed rapid systemic clearance (CL (0.11±0.014) L/h/kg) and small volume of distribution (Vd (0.71±0.14) L/kg). The biological half life (t_1/2) was 56.24 min. After oral administration, alantolactone showed rapid oral absorption in rats, with a short T_max of(45.02±0.88) and (45.13±0.39) min for 14 and 28 mg/kg, respectively.The bioavailability of alantolactone in rats was 50.88%, indicating that alantolactone was orally available.     

Pharmacokinetics of valerenic acid in rats after intravenous and oral administrations

Valerenic acid (VA), a sesquiterpenoid, is one of the major secondary bioactive metabolites of VALERIANA OFFICINALIS L. Until now IN VIVO studies on the absorption, bioavailability, disposition, and metabolism of VA are limited. We established and validated an LC-MS/MS assay for the determination of VA in rat plasma and successfully used this method for pharmacokinetic studies in rats after intravenous (i. v.) and oral administrations. The plasma concentration-time data was analyzed by both non-compartmental and compartmental approaches using WinNonlin software. Following i. v. administration, the disposition of VA in rat plasma was biphasic, subdivided into a fast distribution and a slow elimination phase. The half-life of the distribution phase was 6-12 min, and that of the terminal elimination phase 6-46 h, indicating a possible large tissue binding. Disposition PK of valerenic acid after oral treatment was also described by a two-compartment model with a clearance (CL/F) of 2-5 L · h (-1) · kg (-1) and volume of distribution of (V (d)) 17-20 L · kg (-1). The extent of absorption (F) after oral administration was estimated to be 33.70 % with a half-life of 2.7-5 h. Dose proportionality was observed in terms of dose and AUCs, suggesting linear pharmacokinetics at the dose levels studied in rats.     

Pharmacokinetics and safety of calcium L-threonate in healthy volunteers after single and multiple oral administrations

Aim:

To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers.

Methods:

This was an open-label, single- and multiple-dose study. The subjects were assigned to receive a single dose, 675, 2025, or 4050 mg, of calcium L-threonate (n=12) or repeated doses of 2025 mg twice daily for 4 d (n=12). Serial plasma and urine samples were analyzed with HPLC-MS/MS. Pharmacokinetic parameters of L-threonate were calculated using non-compartmental analysis with WinNonlin software.

Results:

In the single dose group, C_max reached at 2.0 h and the mean t_1/2 was approximately 2.5 h. Area under curve (AUC) and C_max increased with dose escalation, but dose proportionality was not observed over the range of 675 to 4050 mg. AUC and C_max in the fasted subjects were lower compared with those in the non-fasted subjects. Cumulative urinary excretion of L-threonate over 24 h represented 5.9% of the administered dose with a mean Cl/r of 0.8 L/h. In the multiple-dose study, no accumulation appeared upon repeated doses of 2025 mg twice daily for 4 d. There were no serious adverse events that occurred during this study.

Conclusion:

Calcium L-threonate was well tolerated in healthy Chinese subjects, with no pattern of dose-related adverse events. Plasma exposure increased with dose escalation, but linear pharmacokinetics were not observed over the studied doses. L-threonate was absorbed rapidly, and its absorption was enhanced by food intake. No systemic accumulation appeared after repeated administrations.     

人参皂苷-Rg_2在大鼠体内的药代动力学

目的研究人参皂苷-Rg2(ginsenoside-Rg2,GSRG-2)在大鼠体内的药代动力学。方法将健康♂Wister系大鼠(360～420)g随机分组,每组7只,单次尾静脉注射,3个剂量,分别为10、20、50mg·kg-1,从眼眶静脉丛分时取血、处理。采用反相高效液相色谱法、应用外标法测定GSRG-2两个差向异构体SGSRG-2[20(S)-ginsenoside-Rg2]和RGSRG-2[20(R)-ginsenoside-Rg2]在大鼠血浆中的浓度,应用3P87软件计算主要药代动力学参数。结果按10、20、50mg·kg-13个剂量分别单次静脉给药后,SGSRG-2和RGSRG-2在大鼠体内的药代动力学过程符合开放一房室模型,50mg·kg-1剂量组主要药代动力学参数C0、Ke、Vc、T12Ke、AUC和CLs,SGSRG-2分别为77.0478mg·L-1、0.0853min-1、0.6489L、8.1232min、902.9501mg·min·L-1和0.0554L·min-1;RGSRG-2分别为101.7467mg·L-1、0.0675min-1、0.4914L、10.2747min、1508.2185mg.min·L-1和0.0332L·min-1。结论在大鼠体内,SGSRG-2具有代谢不稳定性,部分转化为RGSRG-2;RGSRG-2的消除半衰期较SGSRG-2长。各剂量组中,AUC与给药剂量成正比;SGSRG-2的Ke、T12Ke、Vc和CLs值相近,RGSRG-2的亦相近;但是,SGSRG-2和RGSRG-2两者之间的Ke、T12Ke和CLs的差异有统计学意义(P<0.05)。     

Pharmacokinetics of bumetanide following intravenous, intramuscular, and oral administrations to normal subjects

The pharmacokinetics of bumetanide was studied in 12 normal subjects after 1-mg intravenous, intramuscular, oral solution, and tablet administrations in a random four-treatment crossover design. Plasma and urine concentrations of intact bumetanide were analyzed by a sensitive and specific RIA. The pharmacokinetics of bumetanide after intravenous administration was characterized by a biexponential equation, including an initial disposition phase (t 1/2, alpha = 5.1 min), followed by a slower elimination phase (t 1/2, beta = 44 min). Bumetanide pharmacokinetics after intramuscular and oral administration could be described by a biexponential equation with first-order absorption and elimination. Bumetanide is rapidly absorbed via the intramuscular and oral routes, with mean +/- SD maximum plasma concentrations of 38.2 +/- 9.8 (intramuscular), 34.0 +/- 10.6 (oral solution), and 30.9 +/- 14.6 ng/mL (tablet) achieved within 0.34 +/- 0.23, 0.76 +/- 0.27, and 1.8 +/- 1.2 h after dosing, respectively. The drug is rapidly eliminated from the body after intravenous, intramuscular, oral solution, and oral tablet administrations, with half-lives ranging from 24-86, 47-139, 27-71, and 26-99 min, respectively. Approximately 70% of a parenteral dose and 60% of an oral dose are excreted as intact drug in urine taken 0-24 h after administration. The extent of bioavailability of bumetanide from the tablet and oral solution dosage forms are equivalent, and the absolute bioavailability of the intramuscular and oral preparations are approximately 100 and 80%, respectively. This is consistent with the predicted limited extent of first-pass metabolism after complete absorption of an oral dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

口服和静注丹参素在兔体内的药动学

目的:研究家兔灌胃丹参提取物和静注丹参素溶液后丹参素在体内药动学特征.方法:用高效液相色谱(HPLC)法测定了16只家兔按丹参素10 mg·kg-1单剂量灌胃丹参提取物和静脉注射丹参素溶液后,丹参素血药浓度变化情况.结果:HPLC法的线性范围为0.114～5.68 mg·L-1,r=0.999 8.平均相对回收率为96.8%～101.3%,RSD为1.7%～6.2%,日内、日间精密度RSD分别为3.2%～8.1%和3.3%～8.8% ;经口给药丹参素主要药动学参数T1/2(Ke)为(1.24±0.20 )h,Tmax为(1.25±0.15) h,Cmax为(0.86±0.19 )mg·L-1,AUC(0-7)为(2.95±0.71) mg·h·L-1.静注丹参素主要药动学参数T1/2β为(1.69±0.38) h,AUC(0-7)为(4.37±0.49) mg·L-1·h.结论:经口给药丹参素在兔体内过程符合一室开放模型,吸收较完全,可作为口服应用.     

大鼠静脉注射丹参酚酸B后的药代动力学研究

目的:建立丹参酚酸B的反相高效液相色谱分析方法,并对其在大鼠体内的药代动力学行为特性进行全面的分析研究。方法:生物样品采用液-液萃取方法,以Hypersil C18ODS色谱柱(200 mm×4 .6 mm,5μm) ,柱温40 ℃,流动相:乙腈水=20 80(含0 .25 mol/L乙酸胺) ,用磷酸调pH至4 .0 ,流速:1 .0 mL/min;紫外检测波长:328 nm。结果:鼠尾静脉给予丹参酚酸B1 .6、3 .2、6 .4 mg/kg后,结果显示鼠α相半衰期为(3 .1±0 .1) min,β相半衰期为(31 .5±3 .2) min。大鼠尾静脉给予丹酚酸B后,组织中浓度依次为(高→低) :心、肝、肺、小肠、肾脏、脾、胃、卵巢和脑组织。丹参酚酸B在粪便和尿中24 h及胆汁中2 h的累积排泄百分数分别约为1.43 %、0.77 %及8 .03%。丹参酚酸B人血浆蛋白结合率和大鼠血浆蛋白结合率分别为89 .2 %±1 .8 %和92 .5 %±1 .5 %。结论:本法准确、稳定、灵敏度高,适合生物样品中丹参酚酸B的分析。丹参酚酸B在大鼠体内消除速度快,血浆蛋白结合率较高,胆汁为其主要排泄途径。     

Clinical and pharmacokinetic results with a new ultrashort-acting calcium antagonist, clevidipine, following gradually increasing intravenous doses to healthy volunteers

AIMS: To investigate the tolerability and safety of clevidipine in healthy male volunteers during intravenous infusion at gradually increasing dose rates and to obtain preliminary information on the pharmacokinetics and pharmacodynamic effects of the drug. METHODS: Twenty-five subjects were enrolled in the study and twenty-one of them were included twice, resulting in a total of forty-six study entries encompassing 20 min infusions of clevidipine at target dose rates ranging from 0.12 to 48 nmol min-1 kg-1. Haemodynamic variables and adverse events were recorded throughout the study. Concentrations of clevidipine and its primary metabolite, H 152/81, were followed in whole blood, and the pharmacokinetics were evaluated by non-compartmental and compartmental analysis. An Emax model was fitted to the effect on mean arterial pressure (MAP) over heart rate (HR) and the corresponding blood concentrations of clevidipine. RESULTS: Clevidipine was administered up to a target dose rate of 48 nmol min-1 kg-1, where a pre-determined escape criterion was reached (HR>120 beats min-1 ) and the study was stopped. The most common adverse events were flush and headache, which can be directly related to the mechanism of action of clevidipine. There was a linear relationship between blood concentration and dose rate in the range studied. The median clearance value determined by non-compartmental analysis was 0.125 l min-1 kg-1. Applying the population approach to the sparse data on clevidipine concentrations, an open two compartment pharmacokinetic model was found to be the best model in describing the disposition of the drug. The population mean clearance value determined by this method was 0.121 l min-1 kg-1, and the volume of distribution at steady state was 0.56 l kg-1. The initial half-life, contributing by more than 80% to the total area under the blood concentration-time curve following i.v. bolus administration, was 1.8 min, and the terminal half-life was 9.5 min. At the highest dose rates, MAP was reduced by approximately 10%, and the HR reached the pre-determined escape criterion for this study (>120 beats min-1 ). CONCLUSIONS: Clevidipine is well tolerated and safe in healthy volunteers at dose rates up to at least 48 nmol min-1 kg-1. The pharmacokinetics are linear over a wide dose range. Clevidipine is a high clearance drug with extremely short half-lives. The effect of clevidipine on the blood pressure was marginal, probably due to a compensatory baroreflex activation in this population of healthy volunteers. A simple Emax model adequately describes the relationship between the pharmacodynamic response (MAP/HR) and the blood concentrations of clevidipine.     

诺必擂停在大鼠和Beagle犬体内的药动学研究

目的:研究诺必擂停在大鼠和Beagle犬体内的药动学过程。方法:通过口服和静注两种给药方式,用高效液相色谱法测定血浆中诺必擂停的浓度。结果:大鼠灌胃给予诺必擂停8、16和32 mg/kg剂量后,血药浓度达峰时间tmax分别为20、30、30 min,峰浓度Cmax分别为(300±171)、(468±122)、(982±449)ng/mL,根据血药浓度AUC计算出的生物利用度F为(14.6±2.7)%。Beagle犬按4 mg/kg单剂量口服给予诺必擂停片后,tmax为(95±12)min,Cmax为(436±88)ng/mL,生物利用度F为(27.4±8.4)%。结论:灌胃给药后诺必擂停在大鼠和Beagle犬体内吸收较快但吸收程度较低,该药在两种动物的药动学参数tmax、t1/2α和t1/2β等存在明显的种属差异。     

单次口服阿奇霉素片在中国健康志愿者的药代动力学

目的研究阿奇霉素(大环内酯类抗生素)在中国健康人体的药代动力学。方法 10名健康志愿者单剂量口服阿奇霉素500 mg后,高效液相色谱-紫外检测法测定血清药物浓度;用AIC法结合F检验判别房室模型, DAS程序计算药代动力学参数。结果主要的药代动力学参数:Ka为(0．87 ±0．27)h-1,t1／2β为(39．66±10．85)h,tmax为(2．60±0．52)h,Cmax为(451．19 ±67．72)μg·L-1,CL／F为(0．56±0．13)L·(h·kg)-1,AUC0-144和 AUC0-∞分别为(13．68±2．92)mg·h·L-1和(13．71±2．91)mg·h·L-1。结论最佳房室模型为二室模型。     

Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses

Cobalt has been used by human athletes due to its purported performance‐enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were administered a single intravenous dose of cobalt chloride or cobalt gluconate and serum and urine samples collected for up to 10 days post administration. Cobalt concentrations were measured using inductively coupled plasma mass spectrometry (ICP‐MS) and pharmacokinetic parameters determined. Additional blood samples were collected for measurement of equine EPO concentrations as well as to assess any effects on red blood cell parameters. Horses were observed for adverse effects and heart rate monitored for the first 4 h post administration. Cobalt was characterized by a large volume of distribution (0.939 L/kg) and a prolonged gamma half‐life (156.4 h). Cobalt serum concentrations were still above baseline values at 10 days post administration. A single administration of cobalt had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied and no adverse effects were noted. Based on the prolonged gamma half‐life and prolonged residence time, regulators should be able to detect administration of a single dose of cobalt to horses. Copyright © 2014 John Wiley & Sons, Ltd.