三黄泻心汤中西医结合根除幽门螺杆菌感染的体内外实验研究

目的评价三黄泻心汤与莫西沙星对55株幽门螺杆菌体外联合抗菌效应和临床根除率。方法采用二倍稀释法、棋盘格法和Vitek-32型全自动细菌鉴定仪测定三黄泻心汤与莫西沙星单用或联用对55株幽门螺杆菌的最低抑菌浓度(MIC),计算其联合药敏指数(FIC),绘制药物质量浓度-累积抑菌率曲线;对比观察中西医结合与埃索美拉唑三联方根除幽门螺杆菌感染的疗效。结果试验组与对照组中西药联用对幽门螺杆菌的MIC值均较单用显著降低;试验组FIC不大于0.50,有协同作用,对照组FIC为0.50～0.75,有相加作用;两组药物质量浓度-累积抑菌率曲线向低浓度方向移动联用均较单用明显;观察组和对照组的溃疡愈合率分别为90.91%和78.18%,幽门螺杆菌根除率分别为89.09%和81.82%,两组比较,P<0.01或P<0.05。结论三黄泻心汤中西医结合根除幽门螺杆菌感染的疗效确切,可作为二线治疗方案。     

3种中药提取物对幽门螺杆菌的体外联合抗菌效应研究

目的:研究黄连、蜂胶、吴茱萸对幽门螺杆菌(Hp)的体外联合抗菌效应。方法:采用棋盘法设计,以琼脂平板法测定两两组合的不同浓度中药提取物对Hp的最低抑菌浓度,计算部分抑菌浓度(FIC)指数并判定联合效应。结果:黄连与蜂胶联合应用后,其FIC指数为0.16(<0.5);黄连与吴茱萸联合应用后,其FIC指数为0.63(>0.5);吴茱萸与蜂胶联合应用后,其FIC指数为0.05(<0.5)。结论:黄连与蜂胶联合应用及吴茱萸与蜂胶联合应用,对Hp表现为协同作用,且吴茱萸与蜂胶联合应用协同作用较强;黄连与吴茱萸联合应用,对Hp表现为相加作用;3种中药提取物之间均无拮抗作用。     

头孢羟氨苄与甲氧苄啶联合对葡萄球菌和乙型链球菌的体外抗菌作用

目的观察头孢羟氨苄与甲氧苄啶以不同比例配伍后对葡萄球菌、乙型链球菌抗菌的作用。方法通过2倍稀释法分别测定出乙型溶血性链球菌ATCC32204、金葡菌ATCC26003及临床分离株对头孢羟氨苄与甲氧苄啶的MIC值；用微量棋盘稀释法测出头孢羟氨苄与甲氧苄啶联用后的分级抑菌浓度(FIC)指数和联合杀菌协同系数(T／E)。结果头孢羟氨苄与甲氧苄啶联用后的FIC指数范围为0．2～0．86，联合杀菌协同系数达0．7以上。结论无论从FIC指数还是从杀菌协同系数衡量，头孢羟氨苄与甲氧苄啶联用有协同作用或相加作用，体外抗菌活性明显增强。     

碳青霉烯类抗生素耐药铜绿假单胞菌的体外联合药敏研究

目的评价环丙沙星(CIP)分别与头孢哌酮/舒巴坦(CFS)、哌拉西林/三唑巴坦(TZP)联合用药对临床分离获得的碳青霉烯类抗生素耐药的铜绿假单胞菌(CRPA)的体外抑菌作用。方法采用棋盘法设计,琼脂平板稀释法测定抗菌药物对38株临床分离的CRPA的最低抑菌浓度(MIC),并计算抑菌指数(FIC指数)判断联合抑菌效应。结果 CIP与CFS联用后,5.3%为协同作用,81.5%为相加作用,13.2%为无关作用,没有拮抗作用;CIP与TZP联用后,7.9%为协同作用,73.7%为相加作用,18.4%为无关作用,没有拮抗作用。上述药物联用后,各药MIC50均明显降低,浓度-累积抑菌率曲线均表现为左移。结论 CIP分别与CFS、TZP联用对CRPA体外联合抗菌效应主要表现为协同和相加作用。     

莫西沙星联用头孢哌酮舒巴坦对8种耐药菌的抗菌效应研究

目的探讨莫西沙星与头孢哌酮舒巴坦联用对临床常见耐药菌的抗菌效果。方法采用Vitek-32型全自动细菌鉴定仪,测定莫西沙星与头孢哌酮舒巴坦单用和联用分别对60株金黄色葡萄球菌、大肠埃希菌（ATCC25922）、铜绿假单胞菌、肺炎克雷伯菌和30株粪肠球菌、大肠埃希菌（ATCC35218）、阴沟肠杆菌及幽门螺杆菌的最低抑菌浓度（MIC）,并计算联合药敏指数（FIC值）。结果两药联用对临床分离的360株常见耐药致病菌的MIC均明显降低且抗菌作用增强,对金黄色葡萄球菌、粪肠球菌和幽门螺杆菌的体外抗菌作用为协同作用,对大肠埃希菌（ATCC25922）、铜绿假单胞菌、肺炎克雷伯菌、大肠埃希菌（ATCC35218）和阴沟肠杆菌均为相加作用。结论研究结果对指导医院常见耐药菌感染的治疗具有重要意义。     

万古霉素联合利奈唑胺体外抑制MRSA活性的探讨

目的:探讨万古霉素联合利奈唑胺体外对耐甲氧西林金黄色葡萄球菌(MRSA)抑菌效应。方法:采用试管二倍稀释法测定万古霉素、利奈唑胺及两者联用时对MRSA抑菌的各自最低抑菌浓度(MIC)值,同时利用棋盘微量稀释法测定不同浓度组合的万古霉素、利奈唑胺抗菌药物对MRSA的最低抑菌浓度,计算相应的联合抑菌指数(FIC)。结果:单用抑制MRSA时,MIC万古霉素为1.563μg/m L,MIC利奈唑胺为0.25μg/m L;当两者联用时,MIC万古霉素、MIC利奈唑胺分别为0.391 0μg/m L、0.312 5μg/m L,联用前后MIC差异有统计学意义(P<0.05),其相应的FIC<0.5。结论:万古霉素与利奈唑胺联用有协同抑菌作用,具有较高的体外抗菌活性,可为有效降低临床细菌耐药率提供新途径。     

鱼腥草素钠联合青霉素G对金黄色葡萄球菌的体外抗菌作用研究

目的研究鱼腥草素钠和青霉素G联用对金黄色葡萄球菌的体外抗菌作用。方法用美国临床实验室标准化委员会(CLSI/NCCLS)介绍的方法,使用微量溶液稀释法,分别测得鱼腥草素钠和青霉素G对金黄色葡萄球菌的最低抑菌浓度(Minimum inhibitoryconcentration,MIC);使用棋盘联合药敏试验法,以部分抑菌浓度(fractional inhibitory concentration,FIC)指数为指标,观察鱼腥草素钠和青霉素G联用对金黄色葡萄球菌的抗菌作用。结果鱼腥草素钠对金黄色葡萄球菌的MIC是31.25mg/mL(稀释度1∶32);青霉素G对金黄色葡萄球菌的MIC是0.25U/mL;鱼腥草素钠和青霉素G联用对金黄色葡萄球菌的FIC指数是0.125。结论鱼腥草素钠联用青霉素G对金黄色葡萄球菌联合药敏结果呈协同作用。     

多黏菌素B与其他抗菌药物联用对泛耐药铜绿假单胞菌体外抗菌活性的研究

目的评价多黏菌素B与左氧氟沙星、亚胺培南、哌拉西林/三唑巴坦体外联合应用,对临床分离的30株泛耐药铜绿假单胞菌的抗菌效应。方法采用微量肉汤稀释法、棋盘设计法测定多黏菌素B与左氧氟沙星、亚胺培南及哌拉西林/三唑巴坦单用及联合应用对临床分离的30株泛耐药铜绿假单胞菌的最小抑菌浓度(MIC),并计算FIC指数,判定联合效应:FIC≤0.5为协同作用,0.52.0为拮抗作用。结果多黏菌素B与左氧氟沙星、亚胺培南及哌拉西林/三唑巴坦联用后,各种药物对泛耐药铜绿假单胞菌的MIC值均显著降低,FIC指数在0~0.5、0.5~1的百分率分别为:左氧氟沙星联合组66.67%、26.67%,亚胺培南联合组46.67%、40%,哌拉西林/三唑巴坦联合组60%、33.33%。结论多黏菌素B与左氧氟沙星、亚胺培南、哌拉西林/三唑巴坦联用,对临床分离的30株泛耐药铜绿假单胞菌抗菌作用以协同和相加为主,无拮抗作用。     

广西地桃花水提物与抗菌药物对G+球菌的体外联合抗菌作用

摘 要 目的: 探讨广西地桃花水提物与抗菌药物对G⁺球菌的体外联合抗菌作用。 方法: 采用试管二倍稀释法分别测定地桃花水提物及多种临床常用抗菌药物单药时对金黄色葡萄球菌、粪肠球菌的最小抑菌浓度（MIC）,采用试管棋盘法测定地桃花水提物与抗菌药物联用对金黄色葡萄球菌和粪肠球菌的MIC,并计算联合指数（FIC）。结果:地桃花水提物分别与阿奇霉素、左氧氟沙星合用,对金黄色葡萄球菌的FIC指数分别为0.14、0.28,呈协同作用;与头孢唑林钠、克林霉素合用FIC指数分别为0.75、2.0,依次为相加作用和无关作用。地桃花水提物分别与氨苄西林钠、左氧氟沙星合用,对粪肠球菌的FIC指数分别为0.50、0.27,均为协同作用。结论:地桃花水提物与抗菌药物联用对金葡菌和粪肠球菌的MIC明显下降,呈现不同程度的抗菌效果。     

奥硝唑联用醋酸氯己定对白色念珠菌的体外抗菌活性考察

目的:考察奥硝唑与醋酸氯己定联合用药对白色念珠菌的体外抗菌活性.方法:采用棋盘法设计,琼脂平板稀释法测定最低抑菌浓度 (MIC)值;计算分级抑菌浓度 (FIC)指数并判定联合效应, FIC≤ 0.5为协同作用, 0.5 2为拮抗作用.结果:奥硝唑与醋酸氯己定联合应用,其 MIC显著降低, FIC≤ 0.5.结论:奥硝唑与醋酸氯己定联合用药后,对白色念珠菌体外抗菌活性有协同作用.     

Effects of AMP579 and adenosine on L-type Ca^2＋ current in isolated rat ventricular myocytes

Aim: To compare the effects of AMP579 and adenosine on L-type Ca^2 current (ICa-L) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on ICa-L.Methods: ICa-L was recorded by patch-clamp technique in whole-cell configuration. Results: Adenosine (10nmol/L to 50μmol/L) showed no effect on basal ICa-L, but it inhibited the ICa-L induced by isoproterenol 10nmol/L in a concentration-dependent manner with the IC50 of 13.06μmol/L. Similar to adenosine,AMP579 also showed an inhibitory effect on the ICa-L induced by isoproterenol.AMP579 and adenosine (both in 10μmol/L) suppressed isoproterenol-induced ICa-L by 11.1% and 5.2%, respectively. In addition, AMP579 had a direct inhibitory effect on basal ICa-L in a concentration-dependent manner with IC50(1. 17μmol/L). PD116948 (30μmol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal ICa-L. However, GF109203X (0.4μmol/L), a special protein kinase C (PKC) blocker, could abolish the inhibitory effect of AMP579 on basal ICa-L. So the inhibitory effect of AMP579 on basal ICa-L was induced through activating PKC, but not linked to adenosine A1 receptor. Conclusion:AMP579 shows a stronger inhibitory effect than adenosine on the ICa-L induced by isoproterenol. AMP579 also has a strong inhibitory effect on basal ICa-L in rat ventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal ICa-L at downstream-mechanism.     

CD21和CD40L的表达与血清IgE相关性研究

目的研究哮喘的发病机制,探讨哮喘儿童白细胞表面分化抗原21(CD21)及CD40L的表达与血清IgE的相关性。方法利用流式细胞分析技术检测儿童哮喘发作期及缓解期外周血CD21 、CD40L 的百分率,同时用免疫化学发光法检测血清IgE的水平,并进行相关性分析。结果哮喘发作组CD21 、CD40L 的百分率明显高于哮喘缓解组、肺炎组和正常组(P均<0.01);哮喘发作组IgE明显高于哮喘缓解组、肺炎组和正常组(P均<0.01);哮喘发作组CD21 、CD40L 与IgE呈正相关。结论CD21 、CD40L 的表达与和血清IgE在哮喘的发病机制中发挥重要作用。     

Effects of muscarinic receptor antagonists with or without M2 antagonist activity on cholinergic reflex bronchoconstriction in ovalbumin-sensitized and -challenged mice

To investigate whether the inhibition of muscarinic M(2) receptors results in the enhancement of reflex bronchoconstriction under airway hyperresponsiveness, we evaluated the effects of muscarinic antagonists with or without M(2) antagonist activity on methacholine (MCh)- and SO(2)-induced airway responses in ovalbumin (OVA)-sensitized and -challenged mice. In this model, similar airway hyperresponsiveness to MCh (12 mg/ml) was observed on Days 31 and 37 (2.2-fold and 2.7-fold, respectively). However, airway hyperresponsiveness to SO(2) (0.05 l/min) on Day 37 was less than that on Day 31 (4.0- and 2.7-fold on Days 31 and 37), indicating reflex bronchoconstriction was enhanced on Day 31 in comparison to Day 37. Ipratropium (0.03 - 0.3 mg/ml, inhalation) and Compound A (0.1 - 3 mg/kg, p.o.) inhibited MCh-induced responses on Days 31 and 37. Although ipratropium (0.03 - 1 mg/ml) dose-dependently inhibited SO(2)-induced responses on Day 31, ipratropium at a dose of 0.1 mg/ml significantly increased SO(2)-induced responses on Day 37 (162.2% of the corresponding control). On the other hand, Compound A (0.03 - 0.3 mg/kg, p.o.) inhibited SO(2)-induced responses without any increases on Days 31 and 37. These results suggest that two different conditions of reflex bronchoconstriction are presented in this model: 1) SO(2)-induced responses are enhanced by dysfunctional M(2) receptors on Day 31; 2) the dysfunctional M(2) receptors are partially restored on Day 37. In addition, the inhibition of the restored M(2) receptors further enhance reflex bronchoconstriction.     

Fractionated ifosfamide therapy produces a time-dependent increase in ifosfamide metabolism.

1. Fifteen patients received 1.5 g m-2 of ifosfamide intravenously over 0.5 h every day for 5 days. Twenty-one courses of treatment were studied. Plasma was assayed for ifosfamide by gas liquid chromatography and plasma alkylating activity was measured using the nitrobenzylpyridine (NBP) reaction. 2. A pharmacokinetic analysis revealed a significant decrease in the median (range) elimination half-life of ifosfamide from 7.2 (2.8-14.2) h on day 1 to 4.6 (2.3-7.7) h on day 5 (P less than 0.001, Wilcoxon's test) with a concomitant significant increase in the median (range) clearance from 66 (31-148) ml min-1 on day 1 to 115 (52-381) ml min-1 on day 5 (P less than 0.001). There was no significant change in the volume of distribution on day 5 compared with day 1. 3. There was a highly significant 223% increase in the median (range) plasma nitrobenzylpyridine alkylating activity area under the curve on day 1 from 16 (0.6-105) nmol nor nitrogen mustard equivalents ml-1 h to 52 (13-238) nmol nor nitrogen mustard equivalents ml-1 h on day 5. 4. During five courses of treatment (in five patients in the group) 24 h urine samples were collected on days 1 and 5. The median (range) renal clearance of ifosfamide on day 1 was 6.8 (1.3-16.2) ml min-1 compared with 5.7 (1.3-15.3) ml min-1 on day 5. This difference was not significant. The median (range) metabolic clearance of ifosfamide in these five patients on day 1 was 78.6 (39.9-141.2) ml min-1 and 132.6 (54.6-149.5) ml min-1 on day 5.(ABSTRACT TRUNCATED AT 250 WORDS)     

Allosteric interaction of zinc with recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) GABA(A) receptors

In a recent study we have provided evidence that inhibition of native GABA(A) receptors by zinc depends primarily on the allosteric modulation of receptor gating. Both the kinetics and the sensitivity of the GABA(A) receptor to zinc depend on subunit composition, especially on the presence of the gamma(2) subunit. To analyze the mechanism of action of zinc its effects have been tested on recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors expressed in HEK 293 cells. The currents produced by ultrafast application of GABA have been measured to assess the impact of zinc ions on GABA(A) receptor gating with resolution corresponding to the time scale of synaptic currents. While, as expected, zinc markedly reduced the peak amplitude of alpha(1)beta(2)-mediated currents, its effect on kinetics was significantly different from that observed for alpha(1)beta(2)gamma(2). In particular, unlike alpha(1)beta(2)gamma(2), zinc did not affect the onset of alpha(1)beta(2)-mediated responses. Moreover, zinc increased the extent of desensitisation of alpha(1)beta(2)gamma(2) receptors and reduced desensitisation of alpha(1)beta(2) ones. Quantitative analysis suggests that zinc exerts an allosteric modulation on both alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors. Zinc effects on alpha(1)beta(2)gamma(2) were qualitatively similar to those reported for native receptors.     

结肠运输试验在慢性功能性便秘分型中的价值再评价

目的探讨结肠运输试验方法在慢性功能性便秘分型中的价值。方法采用一次性口服20粒不透X线标志物后每24h连续7d摄片对202例慢性功能性便秘患者进行结肠运输试验。测定全肠道通过时间及其结肠分段时间和传输指数,分别按3d（“3d法”）和7d（“7d法”）诊断标准判断为正常、慢传输型（STC）、出口梗阻型（OOC）和混合型（MC）。结果正常传输型便秘超过半数,“3d法”和“7d法”分别占69%和54%。“3d法”140例全肠道通过时间“正常”者,按“7d法”计算,21%（30/140）结肠分段通过时间延长（则STC）,其中右侧结肠延迟、左侧结肠延迟和左右结肠均延迟分别为67%（20/30）、13%（4/30）和20%（6/30）;未发现OOC。“3d法”诊断为单纯OOC者,“7d法”则大多同时合并存在STC。“7d法”64例STC,右侧结肠延迟、左侧结肠延迟和左右结肠均延迟分别为43%（28/64）、27%（17/64）和30%（19/64）。结论3d法可大致区分肠道通过时间是否延长。“3d法”肠道通过时间延长者,应按7d法计算结肠分段时间以进一步区分STC之具体肠段以及OOC是否合并存在STC或本身为STC。     

Characterization of the endothelin-1-induced regulation of L-type Ca2+ current in rabbit ventricular myocytes

The effects of endothelin-1 (ET-1) on the L-type Ca2+ current (I(Ca)) and the interaction of ET-1 with beta-adrenoceptor stimulation were investigated in rabbit ventricular myocytes by the whole-cell patch-clamp technique. ET-1 (10(-8) M) had a biphasic effect on I(Ca) (direct effect), causing a transient decrease that was followed by a long-lasting increase which is much smaller than the increase induced by isoprenaline (ISO). The effect of ET-1 on I(Ca) was abolished by a selective ET(A) receptor antagonist, FR139317 (10(-6) M). The increase in I(Ca) induced by ET-1 (10(-8) M) was enhanced by a selective ET(B) receptor antagonist, BQ-788 (10(-6) M), as the transient decrease but not the increase in I(Ca) induced by ET-1 (10(-8) M) was suppressed by BQ-788. In the presence of ISO (10(-6) M), ET-1 elicited a more pronounced inhibitory effect: at 10(-9)-10(-7) M ET-1 inhibited the ISO-induced increase in I(Ca) in a concentration-dependent manner (anti-adrenergic effect). The maximum inhibition induced by ET-1 at 10(-7) M was approximately 80% of the ISO-induced response, and the IC50 value for anti-adrenergic effect of ET-1 was 4.2x10(-9) M. The anti-adrenergic effect of ET-1 (10(-8) M) was antagonized by the ET(A) antagonist FR139317 (10(-9)-10(-6) M) in a concentration-dependent manner and was partially inhibited by the ET(B) antagonist BQ-788 (10(-6) M). The anti-adrenergic effect of ET-1 was markedly attenuated by pretreatment of ventricular myocytes with pertussis toxin. The increases in I(Ca) induced by forskolin (10(-6) M), 3-isobutyl-1-methylxanthine (10(-4) M), and 8-bromo-cyclic AMP (3x10(-4) M) were also suppressed by ET-1 (10(-8) M). In summary, ET-1 has a differential effect on I(Ca) in the absence and in the presence of ISO: ET- I has a feeble biphasic action on the baseline I(Ca) and, in addition, it elicits a pronounced anti-adrenergic effect on the ISO-induced increase in I(Ca). Pertussis toxin-sensitive G protein is responsible for the anti-adrenergic effect of ET-1 on I(Ca), but the anti-adrenergic effect of ET-1 may involve also the regulation at the level of signaling process beyond the cyclic AMP generation. Anti-adrenergic effect of ET-1 on I(Ca) is mainly due to activation of ET(A) receptors but ET(B) receptors are also involved partially in the anti-adrenergic effect of ET-1 on I(Ca) in rabbit ventricular myocytes.     

灵芝超微粉对大鼠血液学和血液生化学的影响

目的 研究灵芝超微粉对大鼠血液学和血液生化学的影响.方法 120只大鼠,按体质量随机分为空白对照组(等体积水,A组)和灵芝超微粉高、中、低剂量组[8.4,4.2,2.1 g生药/(kg·24 h),B组,C组,D组],各30只,雌雄兼半.灌胃给药,每日2次,连续91 d,停药后观察30 d.检测大鼠血液学及血液生化学指...     

Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells

The effects of aconitine (ACO), a highly toxic alkaloid, on ion currents in differentiated NG108-15 neuronal cells were investigated in this study. ACO (0.3-30 microM) suppressed the amplitude of delayed rectifier K+ current (I K(DR)) in a concentration-dependent manner with an IC50 value of 3.1 microM. The presence of ACO enhanced the rate and extent of I K(DR) inactivation, although it had no effect on the initial activation phase of I K(DR). It could shift the inactivation curve of I K(DR) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for I K(DR) was also enhanced by ACO. Orphenadrine (30 microM) or methyllycaconitine (30 microM) slightly suppressed I K(DR) without modifying current decay. ACO (10 microM) had an inhibitory effect on voltage-dependent Na+ current (I Na). Under current-clamp recordings, ACO increased the firing and widening of action potentials in these cells. With the aid of the minimal binding scheme, the ACO actions on I K(DR) was quantitatively provided with a dissociation constant of 0.6 microM. A modeled cell was designed to duplicate its inhibitory effect on spontaneous pacemaking. ACO also blocked I K(DR) in neuroblastoma SH-SY5Y cells. Taken together, the experimental data and simulations show that ACO can block delayed rectifier K+ channels of neurons in a concentration- and state-dependent manner. Changes in action potentials induced by ACO in neurons in vivo can be explained mainly by its blocking actions on I K(DR) and I Na.     

Multiple dose study of interactions between artesunate and artemisinin in healthy volunteers

AIMS: To investigate whether coadministration of the antimalarials artesunate and artemisinin alters the clearance of either drug. METHODS: Ten healthy Vietnamese males (Group AS) were randomized to receive a single dose of 100 mg oral artesunate (pro-drug of dihydroartemisinin) on day -5 and then once daily for 5 consecutive days (days 1-5). Oral artemisinin (500 mg) was coadministered on days 1 and 5. Another 10 subjects (Group AM) were given 500 mg oral artemisinin on day -5 and then further doses on days 1-5. Artesunate 100 mg was given on days 1 and 5. Artemisinin and dihydroartemisinin plasma concentrations on days -5, 1 and 5 were quantified by h.p.l.c. with on-line postcolumn derivatization and u.v. detection. RESULTS: In Group AS, dihydroartemisinin oral clearance values (mean (95% CI)) were similar on day 1 (32 (22, 47)) l h(-1) and day 5 (38 (28, 51)) l h(-1) of daily artesunate administration but these mean values were approximately three fold higher compared with day -5 after a single dose (95 (56, 159)). In this group, artemisinin oral clearance increased from 196 (165, 232) l h(-1) on day 1-315 (241, 410) l h(-1) on day 5. In Group AM, dihydroartemisinin oral clearance on day 1 was 39 (34, 46) l h(-1) and increased 1.6 fold to 64 (48, 85) l h(-1) on day 5. In this group, artemisinin oral clearance increased sequentially (1.5 and 4.7 fold, respectively) from 207 (151, 285) l h(-1) on day -5-308 (257, 368) l h(-1) on day 1 and to 981 (678, 1420) l h(-1) on day 5. The increase in artemisinin oral clearance between days -5 and 1 (in the absence of artesunate) was similar to that between days 1 and 5 in Group AS subjects who took daily artesunate. Dihydroartemisinin was not a significant metabolite of artemisinin. CONCLUSIONS: Artesunate (dihydroartemisinin) did not alter the elimination of artemisinin. However, dihydroartemisinin elimination was inhibited by artemisinin. Artemisinin induced its own elimination even 5 days after a single oral dose. There was no evidence for the formation of dihydroartemisinin from artemisinin.