Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis.

Tazarotene (AGN 190168) is a new acetylenic retinoid which is effective for the topical treatment of patients with stable plaque psoriasis and mild to moderate acne vulgaris. Topical gel application provides direct delivery of tazarotene into the skin. At 10 hours after a topical application of 0.1% tazarotene gel to the skin of healthy individuals and patients with psoriasis, approximately 4 to 6% of the dose resided in the stratum corneum and 2% of the dose distributed to the viable epidermis and dermis. Tazarotene is rapidly hydrolysed by esterases to its active metabolite, tazarotenic acid. Tazarotenic acid does not accumulate in adipose tissue, but undergoes further metabolism to its sulfoxide and to other polar metabolites and is rapidly eliminated via both urinary and faecal pathways with a terminal half-life of about 18 hours. Percutaneous absorption is similar between healthy individuals and patients with facial acne, leading to plasma concentrations below 1 microg/L. The systemic bioavailability of tazarotene (measured as tazarotenic acid) is low, approximately 1% after single and multiple topical applications to healthy skin. In patients with psoriasis under typical conditions of use, systemic bioavailability increased during the initial 2 weeks of treatment from 1% (single dose) to 5% or less (steady state). The increased bioavailability is probably related to decreases in plaque elevation and scaling due to successful treatment, resulting in a less effective skin penetration barrier to tazarotene. Steady-state concentrations of tazarotenic acid are achieved within 2 weeks of topical treatment in both healthy and psoriatic skin types. The large variability in plasma concentrations observed in patients with psoriasis is probably because of the large differences in lesional skin condition, the amount of drug applied and the surface area of application. There was no significant drug accumulation in the body with long term treatment of patients with psoriasis. Topical administration of tazarotene requires dosages much smaller than those usually required for oral retinoids, such as isotretinoin, acitretin and etretinate, and it delivers the drug directly into the target skin tissues. The low systemic absorption and rapid systemic elimination of tazarotene and tazarotenic acid results in limited systemic exposure. Thus, topical tazarotene has a low potential for systemic adverse effects and is effective in the treatment of patients with acne and psoriasis.     

他扎罗汀乳膏与阿达帕林凝胶随机对照治疗寻常型痤疮多中心临床试验

目的 评价国产0．1％他扎罗汀乳膏治疗面部轻中度寻常型痤疮的疗效及安全性。方法 用多中心、随机单盲对照试验方法，0．1％他扎罗汀乳膏或0．1％阿达帕林凝胶局部外用每日1次，疗程8周。在治疗前、治疗2，4和8周进行观察。入选病例142例，其中0．1％他扎罗汀乳膏组71例，完成8周观察64例。0．1％阿达帕林凝胶组71例，完成8周观察67例。结果他扎罗汀乳膏组有效率72．3％，阿达帕林凝胶组有效率62．7％。两组之间无显著统计学差异。两组的不良反应均表现为轻度到中度的局部刺激，发生率分别为28．70％和23．50％。结论 他扎罗汀乳膏治疗寻常型痤疮安全有效。     

Tazarotene does not affect the pharmacokinetics and efficacy of a norethindrone/ethinylestradiol oral contraceptive

OBJECTIVE: To determine the pharmacokinetic and pharmacodynamic interaction between oral tazarotene and an oral contraceptive containing norethindrone 1mg and ethinylestradiol 0.035 mg (Ortho-Novum 1/35).DESIGN: Two separate open-label, parallel-group, single-centre, pharmacokinetic and pharmacodynamic interaction studies.PARTICIPANTS AND METHODS: Twenty-seven healthy women (age 20-55 years) completed Study I, with a duration of 64 days during three consecutive menstrual cycles. Ortho-Novum 1/35 was taken once daily from study day 0 (first cycle day 1) to day 61 (third cycle day 6), and oral tazarotene 1.1 mg was coadministered daily from study day 34 (second cycle day 7) to day 61. Twenty-nine healthy women (age 20-44 years) completed Study II, with a duration of 75 days during three consecutive menstrual cycles. Ortho-Novum 1/35 was taken once daily from study day 0 (first cycle day 1) to day 74 (third cycle day 19), and oral tazarotene 6 mg was coadministered daily from study day 48 (second cycle day 21) to day 74. In both studies, the pharmacokinetics of tazarotenic acid on study day 61 (third cycle day 6) were evaluated from plasma tazarotenic acid concentrations. Pharmacokinetic parameters of plasma norethindrone and ethinylestradiol were compared before and after tazarotene administration (cycle day 6 of the second and third cycles, respectively). Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations were compared before and after tazarotene administration (cycle days 2, 4 and 6 of the second and third cycles, respectively). In Study II, serum progesterone concentrations were also determined on cycle days 18 and 20 of the second and third cycles. Tazarotenic acid was determined by liquid chromatography-tandem mass spectrometry. Ethinylestradiol and norethindrone were determined by gas chromatography-mass spectrometry. LH and FSH were assayed by microparticle enzyme immunoassay in Study I and by double-antibody radioimmunoassay in Study II. Progesterone was determined by solid-phase radioimmunoassay.RESULTS: In Study I (tazarotene 1.1 mg), the area under the plasma concentration-time curve from zero to 24 hours (AUC24) and the peak concentration in plasma (Cmax) for tazarotenic acid were 121 +/- 27 microg. h/L and 28.9 +/- 9.4 microg/L (mean +/- SD), respectively. In Study II (tazarotene 6 mg), AUC24 and Cmax for tazarotenic acid were 379 +/- 78 microg. h/L and 111 +/- 37 microg/L (mean +/- SD), respectively. In both studies, for both norethindrone and ethinylestradiol, the 90% CIs of AUC24 and Cmax on cycle day 6 before and after tazarotene administration were within the 80-125% boundary. In Study I, the 90% CIs of serum FSH and LH concentrations on cycle day 4 were within the 80-125% boundary. FSH and LH concentrations on cycle day 6 were marginally/partially outside the 80-125% boundary as a result of high variability. However, the mean FSH and LH serum concentrations on cycle day 6 of the third cycle were lower than those of the second cycle. In Study II, the 90% CIs of serum FSH, LH and progesterone concentrations were all within the 80-125% boundary, except for LH on cycle day 2. LH concentrations on cycle day 2 were marginally/partially outside the 80-125% boundary as a result of high variability. However, the mean serum LH concentration on cycle day 2 of the third cycle was lower than that of the second cycle.CONCLUSIONS: Oral tazarotene up to 6 mg once daily does not affect the pharmacokinetics and efficacy of Ortho-Novum 1/35.     

Disposition and biotransformation of the acetylenic retinoid tazarotene in humans

Oral tazarotene, an acetylenic retinoid, is in clinical development for the treatment of psoriasis. The disposition and biotransformation of tazarotene were investigated in six healthy male volunteers, following a single oral administration of a 6 mg (100 microCi) dose of [14C]tazarotene, in a gelatin capsule. Blood levels of radioactivity peaked 2 h postdose and then rapidly declined. Total recovery of radioactivity was 89.2+/-8.0% of the administered dose, with 26.1+/-4.2% in urine and 63.0+/-7.0% in feces, within 7 days of dosing. Only tazarotenic acid, the principle active metabolite formed via esterase hydrolysis of tazarotene, was detected in blood. One major urinary oxidative metabolite, tazarotenic acid sulfoxide, accounted for 19.2+/-3.0% of the dose. The majority of radioactivity recovered in the feces was attributed to tazarotenic acid representing 46.9+/-9.9% of the dose and only 5.82+/-3.84% of dose was excreted as unchanged tazarotene. Thus following oral administration, tazarotene was rapidly absorbed and underwent extensive hydrolysis to tazarotenic acid, the major circulating species in the blood that was then excreted unchanged in feces. A smaller fraction of tazarotenic acid was further metabolized to an inactive sulfoxide that was excreted in the urine.     

Adapalene: a review of its use in the treatment of acne vulgaris

Adapalene (Differin) is a retinoid agent indicated for the topical treatment of acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel. It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment. Adapalene has a rapid onset of action and a particularly favourable tolerability profile compared with other retinoids. These attributes can potentially promote patient compliance, an important factor in treatment success. Adapalene is, therefore, assured of a role in the first-line treatment of acne vulgaris.     

他扎罗汀乳膏治疗痤疮的临床疗效观察

目的:为痤疮患者提供更好的治疗方案。方法:122例痤疮患者按随机单盲对照原则分为他扎罗汀组(42例)、水氯酊组(38例)和联合治疗组(42例),连续外用8周后观察疗效。结果:3组皮损数均随治疗时间的延长而逐渐减少,与治疗前比较,治疗8周后皮损总分3组差异均有统计学意义(P<0.05或P<0.01)。治疗8周后有效率,他扎罗汀组与水氯酊组比较差异有统计学意义(χ2=17.629,P<0.05);联合治疗组与水氯酊组比较差异也有统计学意义(χ2=15.532,P<0.05);他扎罗汀组与联合治疗组比较差异无统计学意义(χ2=10.130,P>0.05)。结论:对于非炎症性痤疮可单用他扎罗汀治疗;对脓疱型患者水氯酊效果优于他扎罗汀,考虑与氯霉素的抗菌作用有关;而对于炎症性痤疮可选用他扎罗汀加0.5%水氯酊外用。     

Tazarotene cream versus adapalene cream in the treatment of facial acne vulgaris: a multicenter, double-blind, randomized, parallel-group study

A multicenter, double-blind, randomized, parallel-group trial compared tazarotene 0.1% cream with adapalene 0.1% cream, once daily for 12 weeks, in 173 patients with facial acne vulgaris. Tazarotene was associated with a significantly greater incidence of patients achieving 50% or greater global improvement (77% vs. 55%, P < or = .01), and a significantly greater reduction in comedo count (median of 68% vs. 36%, P < or =.001, compared with adapalene. A significant between-group difference in baseline inflammatory lesion count precluded a comparison of efficacy against inflammatory acne. The most common adverse events were dryness, peeling/flaking, itching, redness/erythema, burning, and facial irritation with comparable incidences of each between groups. Mean peeling and burning levels were milder with adapalene, though were trace or less in both groups throughout. There were no significant between-group differences in the incidence of patients discontinuing due to lack of efficacy or adverse events. Tazarotene cream offers significantly greater efficacy and comparable tolerability to adapalene cream.     

他扎罗汀倍他米松乳膏对小型猪经皮给药后的系统吸收及其相互作用研究

目的：通过与已上市单方他扎罗汀凝胶（tazarotene gel）和二丙酸倍他米松乳膏（betamethasone dipropionate cream）比较，研究新的复方制剂他扎罗汀倍他米松乳膏（tazarotene and betamethasone dipropionate cream，简称"复方"）对小型猪经皮给药后的药物吸收以及药物组分间吸收的相互影响。方法：将18只小型猪随机分入复方组、他扎罗汀凝胶组和二丙酸倍他米松乳膏组，每组6只。小型猪按20%的体表面积2 mg·cm^-2给予相应组别的药物，并在给药后24 h清除药物。分别于给药前和给药后不同时间点采集血样。高效液相色谱-串联质谱（liquid chromatography-tandem mass spectrometry，LC-MS/MS）法测定血浆中他扎罗汀及其代谢物他扎罗汀酸和/或二丙酸倍他米松及其代谢物倍他米松的浓度。DAS 2.1.1软件进行药代动力学（pharmacokinetic，PK）参数计算并统计分析。结果：复方他扎罗汀倍他米松乳膏与单方他扎罗汀凝胶中的他扎罗汀均不易透过小型猪皮肤到达血液，系统吸收非常低，而复方组血浆中的他扎罗汀及其活性代谢产物他扎罗汀酸较单方组更低；复方他扎罗汀倍他米松乳膏和二丙酸倍他米松乳膏中的二丙酸倍他米松几乎不透过小型猪皮肤到达血液，系统吸收非常低，其中复方组与单方组中二丙酸倍他米松及其代谢产物倍他米松到达血液的量未见明显的差异。结论：复方制剂中他扎罗汀对二丙酸倍他米松的系统吸收未产生相互作用，而二丙酸倍他米松对他扎罗汀的系统吸收产生了有益的相互作用，有利于用药安全。     

Tazarotene versus tazarotene plus clindamycin/benzoyl peroxide in the treatment of acne vulgaris: a multicenter, double-blind, randomized parallel-group trial

Topical retinoids offer highly effective treatment for both inflammatory and non-inflammatory acne, with tazarotene demonstrating greater efficacy than other topical retinoids. A multicenter, double-blind, randomized, parallel-group trial has been performed to evaluate whether the adjunctive use of clindamycin/benzoyl peroxide could enhance the efficacy of tazarotene still further. Patients with moderate to severe inflammatory acne applied tazarotene 0.1% cream each evening and were randomly assigned to morning applications of vehicle gel or a ready-to-dispense formulation of clindamycin 1%/benzoyl peroxide 5 % gel containing 2 emollients. Tazarotene/clindamycin/benzoyl peroxide achieved a significantly greater reduction in comedo count than tazarotene monotherapy and, among patients with a baseline papule plus pustule count of > or =25 (the median value), a significantly greater reduction in inflammatory lesion count. The combination therapy was also at least as well-tolerated as tazarotene monotherapy. The adjunctive use of clindamycin/benzoyl peroxide gel with tazarotene cream promotes greater efficacy and may also enhance tolerability. Any improvements in tolerability could be due to the emollients in the clindamycin/benzoyl peroxide gel formulation.     

Study of the percutaneous penetration of flurbiprofen by cutaneous and subcutaneous microdialysis after iontophoretic delivery in rat

The percutaneous penetration of flurbiprofen delivered by iontophoresis was investigated in the hairless rat. Unbound concentrations of flurbiprofen in dermis and subcutaneous tissue were continuously measured by on-line microdialysis. Simultaneously, a conventional blood sampling was performed. Linear microdialysis probes were implanted in dermis and in subcutaneous tissue at a depth of 398.3 +/- 15.3 and 1878 +/- 35.8 microm, respectively. Commercial patches were used to deliver flurbiprofen for 15 min at a current density of 0.4 mA/cm(2). In vivo recoveries of both probes, determined by using naproxen as retrodialysis calibrator, were 26.0 +/- 0.3 and 72.9 +/- 0.7% for dermal and subcutaneous probe, respectively. After iontophoretic delivery, a gradient in mean tissue unbound concentrations was observed, with a C(max) in dermis of 8.7 +/- 0.4 microg/mL as compared with subcutaneous C(max) of 0.5 +/- 0.1 microg/mL. The area under the unbound concentration curve in dermis was 13-fold higher than that in the subcutaneous tissue. Total plasma concentration curves showed a rapid absorption phase with a T(max) of 30 min and C(max) of 1.8 +/- 0.1 microg/mL. In conclusion, iontophoresis delivery was demonstrated to be efficient to deliver a high amount of flurbiprofen in dermis and underlying tissue with a fast input rate whereas maintaining a low plasma exposure.     

复方痤疮微乳膏中阿奇霉素的萃取与测定

目的：建立复方痤疮微乳膏中阿奇霉素的萃取与测定方法。方法：精密称取复方痤疮微乳膏,精密加入三氯甲烷使溶解完全;精密加入0.1mol·L-1盐酸溶液,振荡5min,静置15min。定量吸取萃取液,用0.1mol·L-1盐酸溶液定容。精密量取5mL,与85%硫酸溶液5mL混合,振摇1min,室温下放置30min。分光光度法测定λ482nm处的吸光度。结果：阿奇霉素浓度在25~65μg·mL-1范围内线性相关性好（r=0.9996,n=5）。盐酸溶液萃取阿奇霉素的回收率为92.86%,精密度RSD为0.91%（n=9）。制剂中其他成分和辅料不干扰测定,样品测定重现性好（RSD=0.89%,n=5）。结论：该方法简单、快速、经济,适用于复方痤疮微乳膏中阿奇霉素的质量控制。     

Essential oil of croton nepetaefolius and its main constituent, 1,8-cineole, block excitability of rat sciatic nerve in vitro

1. The effects of the essential oil of Croton nepetaefolius (EOCN) and its major constituent, 1,8-cineole, on the compound action potential (CAP) of nerve were investigated. 2. Experiments were performed in sciatic nerves dissected from Wistar rats, mounted in a moist chamber and stimulated at a frequency of 0.2 Hz, with electric pulses of 100 micros duration at 20-40 V. Evoked CAP were displayed on an oscilloscope and recorded on a computer. The CAP control parameters were as follows: peak-to-peak amplitude 8.1 +/- 0.6 mV (n = 15); conduction velocity 83.3 +/- 4.2 m/s (n = 15); chronaxie 58.0 +/- 6.8 msec (n = 6); and rheobase 2.8 +/- 0.1 V (n = 6). 3. Lower concentrations of EOCN (100 and 300 microg/mL) and 1,8-cineole (153 and 307 microg/mL; i.e. 1 and 2 mmol/L, respectively) had no significant effects on CAP control parameters throughout the entire recording period. However, at the end of 180 min exposure of the nerve to the drug, peak-to-peak amplitude was significantly (P < 0.05) reduced to 27.4 +/- 6.7 and 1.7 +/- 0.8% of control values by 500 and 1000 microg/mL EOCN, respectively (n = 6), and to 76.5 +/- 4.4, 70.0 +/- 3.9 and 14.8 +/- 4.1% of control values by 614, 920 and 1227 microg/mL (i.e. 4, 6 and 8 mmol/L) 1,8-cineole, respectively (n = 6). Regarding conduction velocity, at the end of the 180 min exposure period, this parameter was significantly reduced to 85.8 +/- 7.3 and 48.7 +/- 12.3% (n = 6) of control values by 500 and 1000 microg/mL EOCN, respectively, and to 86.4 +/- 4.5 and 76.1 +/- 5.2% (n = 6) by 920 and 1227 microg/mL 1,8-cineole, respectively. Chronaxie and rheobase were significantly increased by the higher concentrations of both EOCN and 1,8-cineole. 4. It is concluded that EOCN and its main constituent 1,8-cineole block nerve excitability in a concentration-dependent manner, an effect that was totally reversible with 1,8-cineole but not with EOCN. This suggests that other constituents of EOCN, in addition to 1,8-cineole, may contribute to the mediation of this effect of EOCN.     

Tolerability comparison of adapalene gel, 0.3% versus tazarotene cream, 0.05% in subjects with healthy skin

BACKGROUND: Topical retinoids, including adapalene and tazarotene, are a primary treatment choice for patients with acne. Adapalene is currently marketed in a 0.1% concentration in gel and cream formulation. A new gel containing a higher concentration (0.3%) of adapalene has been developed. In clinical studies, adapalene 0.1% concentration has proven to be better tolerated than other retinoids in skin treatment. However, the tolerability of adapalene gel 0.3% has yet to be compared to other topical retinoids. PURPOSE: The purpose of this study was to compare the local cutaneous tolerability of adapalene gel 0.3% once daily versus tazarotene cream 0.05% once daily. METHODS: Subjects reported to the investigative site each day Monday through Friday, cleansed the faced and then applied adapalene 0.3% gel to one side of the face and tazarotene 0.05% cream to the other in the presence of study personnel. For the weekends, subjects were instructed to apply the treatment at home according to the same procedure. Tolerability was assessed during each weekday visit. The study lasted for 3 weeks. RESULTS: Tolerability results for adapalene 0.3% gel and tazarotene 0.05% cream were statistically similar throughout the study. Investigator-assessed overall tolerability was in favor of adapalene at days 19 and 22 (P=.043). A cosmetic acceptability survey also showed results were better for adapalene 0.3% gel. CONCLUSION: Adapalene gel 0.3% is very well-tolerated with good cosmetic acceptability.     

复方乳铁蛋白-乳酸过氧化酶洗剂及其乳霜治疗寻常型痤疮的前瞻性研究

目的评价复方乳铁蛋白-乳酸过氧化酶洗剂及其乳霜对寻常型痤疮患者的疗效及安全性。方法选取63例轻、中度寻常型痤疮患者,用复方乳铁蛋白-乳酸过氧化酶洗剂清洗后,外用复方乳铁蛋白-乳酸过氧化酶乳霜,bid,疗程4 wk。观察治疗前以及治疗后wk 1、2、4皮损变化。疗程结束后完成调查问卷。结果随着使用时间延长,痤疮的各类皮损数目逐渐减少。对靶区内所有皮损的疗效观察表明,痊愈5例(8．3％),显效26例(43．3％),总有效率达51．6％。其中,炎性丘疹和脓疱明显减少,4 wk后治疗炎性丘疹和脓疱的总有效率达63．4％。有78．3％的患者认为其皮肤出油情况得以改善。不良事件有18例,除3例提前退出试验外,余15例反应轻微且自行消退。结论联合应用复方乳铁蛋白-乳酸过氧化酶洗剂及其乳霜能有效、安全地治疗轻中度的寻常型痤疮。     

Spatial distribution of 8-methoxypsoralen penetration into human skin after systemic or topical administration

AIMS: Photochemotherapy employing psoralens combined with UVA irradiation (PUVA) is a standard therapy for a variety of dermatoses. Psoralens can be administered orally or topically in the form of bath or cream preparations. Recommendations for the time of UVA irradiation are mainly based on the time course of minimal phototoxic doses. However, the time course and depth of skin penetration of psoralens is not well characterized. METHODS: We assessed the time course of 8-MOP concentrations in horizontal epidermal and dermal skin sections in 10 patients undergoing oral (n = 3), cream (n = 4) and bath (n = 3) PUVA therapy. Punch biopsies (4 mm) were taken from "healthy" skin sites. A highly sensitive LC-MS-MS method was employed for 8-MOP analysis. RESULTS: Epidermal concentrations following cream or bath were highest at the end of the application period (time zero) when irradiation is performed. At this time, 8-MOP cream provided significantly higher epidermal concentrations (mean +/- s.e. mean 128.0 +/- 22.6 pg mm-3; 95% CI: 77.6, 178.4) than oral 8-MOP (27.0 +/- 25.3 pg mm-3; 95% CI: 29.3, 83.3 at 1 h; P = 0.025). Conversely, concentrations in the papillary dermis were significantly higher with oral 8-MOP (20.2 +/- 3.1 and 16.2 +/- 2.2 pg mm-3 at 1 and 2 h, respectively) than with 8-MOP cream (7.1 +/- 2.8 and 8.4 +/- 2.0 pg mm-3 time zero and 0.5 h, respectively; P = 0.020 and 0.045, respectively) or bath (8.8 +/- 3.1 and 7.7 +/- 2.2 pg mm-3; P = 0.050 and 0.039, respectively). The observed time courses of 8-MOP concentrations correspond to time courses of photosensitivity found previously with the different treatment modalities. CONCLUSIONS: The higher epidermal 8-MOP concentrations found after topical 8-MOP may explain the lower UVA doses needed with the topical route. These results suggest that topical 8-MOP may be superior in patients where the pathology is localized in the epidermis. In sclerosing diseases, which mainly affect the dermis oral PUVA might be advantageous because dermal concentrations are highest with this route of administration.     

固相萃取结合HPLC-MS测定人血浆中奥曲肽的浓度及相对生物利用度固相萃取结合HPLC-MS测定人血浆中奥曲肽的浓度及相对生物利用度

目的建立人血浆中奥曲肽浓度的HPLC-MS测定法，研究国产奥曲肽注射剂的人体生物利用度。方法 血浆样品用HPL 1cc固相萃取小柱萃取，经Waters Xetrra C₁₈ MS分离后测定。18名健康志愿受试者采用随机交叉试验设计，分别im奥曲肽试验制剂和参比制剂200 μg，不同时间点采血，比较两者的生物利用度。结果线性范围0.5～40 μg·L^-1，方法回收率为97.1%～100.5%。日内、日间RSD分别为1.1%～1.6%，2.9%～4.8%。单剂量im奥曲肽200 μg后两种制剂的C_max分别为（19±10） μg·L^-1和（19±11） μg·L^-1，t_max分别为（0.50±0.15） h和（0.52±0.20） h；AUC_0～7h分别为（50±25） h·μg·L^-1和（50±25） h·μg·L^-1，t_1/2分别为(1.5±0.8) h 和(1.5±0.8) h。二者之间均无显著性差异，以进口奥曲肽为参比制剂，国产奥曲肽注射液的相对生物利用度为101%±10%。结论该方法灵敏、准确度高，可用于奥曲肽体内过程研究。两注射剂为生物等效性制剂。     

复方木尼孜其颗粒治疗寻常型痤疮的临床研究

目的：探讨复方木尼孜其颗粒治疗寻常型痤疮的临床疗效和安全性。方法：215例患者随机分为观察组114例和对照组101例,观察组采用复方木尼孜其颗粒和夫西地酸乳膏治疗,对照组采用异维A酸胶囊和夫西地酸乳膏,治疗结束后观察疗效。结果：观察组有效率为96.49%,治愈率为57.02%;对照组有效率为92.08%,治愈率为54.46%,两组患者的总有效率和治愈率比较无显著性差异（P〉0.05）;但是观察组患者的不良反应率为16.67%,明显低于对照组的91.09%（P〈0.01）。结论：复方木尼孜其颗粒治疗寻常型痤疮疗效与异维A酸胶囊相当,但不良反应发生率明显较低,值得临床推广应用。     

Determination of chlorogenic acid in rat plasma by high performance chromatography after peritoneal administration of compound Daqingye injection

A simple and sensitive high performance liquid chromatographic method has been developed for the determination of chlorogenic acid (3-O-caffeoyl-D-quinic acid) in rat plasma and applied to its pharmacokinetic study in rats after peritoneal administration of compound Daqingye injection. Plasma samples are extracted with perchloric acid. HPLC analysis of the chlorogenic acid is performed on a C(18) reversed-phase column using methanol-water (80: 20, v/v, pH 2.8) as mobile phase with UV detector set at 327 nm. The standard curves are linear in the range of 0.200-10.0 microg/ml (r=0.9982). The inter- and intra-day precision (relative standard deviation) was less than 9% and the accuracy (relative error) was less than 10%. The limit of quantitation was 0.200 microg/ml. The plasma concentration of chlorogenic acid shows a C(max) of 7.53+/-0.52 microg/ml at 13.33+/-4.00 min with a t(1/2) of 59.10+/-5.42 min.     

HPLC determination of chondrosine in mouse blood plasma after intravenous or oral dose

The bioavailability of chondrosine was evaluated by its direct measurement as found in the blood plasma following removal of plasma proteins by perchloric acid. The postcolumn HPLC determination of chondrosine was performed on an SCX column (6 mm i.d.x 150 mm), 0.35 mol/l boric acid (pH 5.2 adjusted by 0.1 mol/l NaOH) as an eluent (0.9 ml/min), 0.5% 2-cyanoacetamide and 1.0 M NaOH as fluorogenic reagents (0.25 ml/min each) with a fluorescence detector (ex. 331nm, em. 383nm). Two separate animal studies were conducted. In study 1, adult male ddY mice (n=6) received i.v. chondrosine (1.0 mg/kg body weight) and the plasma samples were collected. In the second study, 6 adult male ddY mice received p.o. chondrosine (400 mg/kg body weight) and the plasma samples were collected. Blood plasma samples were deproteinized by perchloric acid, analyzed and the bioavailability of chondrosine was determined. Twenty five to fifty microliters of blood plasma were required for the assay. Chondrosine was absorbed after oral administration with two phases having two maximum values, 7.8+/-5.4 and 4.0+/-1.9 at 15 microg/ml and 120 min, respectively; it disappeared from the blood flow very quickly after intravenous administration. This study provides the first report of the bioavailability of orally administered chondrosine in mice.