The pharmacokinetics,safety and tolerability of the co-administration of diethylcarbamazine and albendazole

The pharmacokinetics, safety and tolerability of single, oral doses of diethylcarbamazine (DEC) and albendazole, given alone or in combination, were investigated in a double-blind, randomized and placebo-controlled trial involving 42 amicrofilaraemic subjects living in an area of India where lymphatic filariasis is endemic. The subjects (34 males and eight females, aged 18-52 years and weighing 46-66.5 kg) were randomly allocated to one of the three drug groups. Fourteen were given just DEC (6 mg/kg), another 14 were given just albendazole (400 mg) and the remaining 14 were given both DEC (6 mg/kg) and albendazole (400 mg). Blood samples for pharmacokinetic study were collected at specified intervals before and after drug administration. Plasma concentrations of DEC and albendazole/albendazole sulphoxide were estimated using gas chromatography and HPLC, respectively. The safety and tolerability of the treatments were evaluated through clinical and laboratory assessments. Both the DEC and albendazole were well tolerated when given alone or in combination, no adverse events being observed. In all three treatment groups, the drugs were rapidly absorbed from the gastro-intestinal tract although there was marked inter-individual#10; variation. The pharmacokinetics of DEC, albendazole and albendazole sulphoxide were similar, whether each drug was given alone or in combination. These results indicate that there is no adverse pharmacokinetic or pharmacodynamic reason why DEC and albendazole should not be co-administered to control lymphatic filariasis.     

A comparative trial of albendazole alone versus combination of albendazole and praziquantel for treatment of Trichuris trichiura infection

A randomized clinical trial was conducted to compare the effectiveness of albendazole alone and albendazole combined with praziquantel in the treatment of Trichuris trichiura infection. The drug regimens consisted of single dose of albendazole 400 mg (A1, n=34), 3 days of albendazole 400 mg daily (A3, n=34), 5 days of albendazole 400 mg daily (A5, n=35), single dose of albendazole 400 mg plus praziquantel 40 mg/kg (AIP1, n=34), and 3 days of albendazole 400 mg plus praziquantel 40 mg/kg daily (A3P3, n=36). It was found that treatment with 3 or more consecutive days of albendazole with or without praziquantel resulted in a significant reduction in density of Trichuris eggs in stools while a single dose of such drug did not. Praziquantel was not shown to have synergistic or antagonistic effects with albendazole. A regimen of 400 mg of albendazole daily for 3 days was found to be the most suitable therapy for Trichuris infection.     

Albendazole plus praziquantel versus albendazole alone as a pre-operative treatment in intra-abdominal hydatidosis caused by Echinococcus granulosus

Summary objective  To compare the effects of a combined medication of albendazole (10 mg/kg/day) plus praziquantel (25 mg/kg/day) to those of albendazole alone at different doses (10 and 20 mg/kg/day).
method  The protoscoleces9 viability was studied in a consecutive series of patients affected by intra-abdominal hydatidosis caused by Echinococcus granulosus . In all cases the drugs were given during the month prior to surgery.
results  A significant increase of patients with nonviable protoscoleces was observed in the group treated with the scolicides combination compared to those treated with albendazole alone, both at a dose of 10 mg/kg/day ( P = 0.004) and at a dose of 20 mg/kg/day ( P = 0.03). Albendazole sulphoxide levels in serum and in cyst fluid were higher in patients given the combined therapy than in those who received only albendazole (10 mg/kg/day: P = 0.016; 20 mg/kg/day: P = 0.034). Levels in the cysts were not significantly different probably due to the sample size; nevertheless a lineal relation between the values obtained in serum and inside the cysts could be discerned in the patients treated with the combined medication.
conclusion  Albendazole plus praziquantel is more effective than monotherapy with albendazole in the preoperative treatment of intra-abdominal hydatidosis.     

Determination of the minmum effective dosages of praziquantel, albendazole, and mebendazole against Clonorchis sinensis infection in rats

In order to determine the minimum effective dosages of praziquantel, albendazole, and mebendazole against Clonorchis sinensis infection in Sprague-Dawley rats, each rat was infected with 30 metacercariae and treated with one of three drugs. The rats were killed and examined 25 days after praziquantel treatment or 11 days after albendazole or mebendazole treatment. The minimum effective dosages were a single dose of praziquantel 375 mg/kg, albendazole 150 mg/kg, and mebendazole 150 mg/kg. Trials are required to determine whether these dosages are useful in the treatment of human clonorchiasis.     

Single-dose therapy for giardiasis in school-age children

A randomized controlled trial was carried out to study the efficacy of combined albendazole and praziquantel in the treatment of giardiasis in school-age children. Eighty-four children were randomly allocated to 3 groups: group 1 (n = 31) albendazole 400 mg combined with praziquantel 20 mg/kg; group 2 (n = 26) albendazole 800 mg as a single dose; group 3 (n = 27) tinidazole 50 mg/kg as a single dose. The treatment was considered curative when Giardia was not found in two consecutive stool samples. The parasitological cure rate was 74.2% for combined single-dose albendazole-praziquantel, 50% and 92.6% in the albendazole and tinidazole groups respectively (p = 0.0023). There was no statistically significant difference between the cure rates of the combined regimen and tinidazole (p > 0.05). This combined regimen was considered safe, with only minor side-effects being observed. Of the single-dose regimens, tinidazole still achieves the highest parasitological cure rate for giardiasis. The albendazole-praziquantel combined regimen may be an alternative single-dose therapy for giardiasis in children, especially as this combination will eradicate common intestinal protozoa and co-existing helminths. Whether the dosage of this combination treatment should be adjusted for G. intestinalis remains to be established by further study.     

Intravenous busulphan for conditioning before autologous or allogeneic human blood stem cell transplantation

This study was undertaken to evaluate the toxicity and pharmacokinetics of a dimethyl sulphoxide (DMSO)-based intravenous formulation of busulphan in the conditioning of 45 patients undergoing allogeneic or autologous stem cell transplantation (SCT). Busulphan was given as a single daily dose. In 15 patients a single dose of intravenous busulphan, given over 3 h in 1 d, was combined with additional oral (single daily) doses. Thirty patients received all four daily doses intravenously. Busulphan plasma levels were analysed using high performance liquid chromatography. There was no major acute toxicity with daily intravenous doses of 2.8-3.1 mg/kg infused over 3 h. No veno-occlusive disease (VOD) was seen in 30 patients receiving busulphan as an intravenous formulation over 4 d. In the group of 15 patients receiving three oral doses and one intravenous single daily dose, one patient experienced mild VOD. Pharmacokinetic samples were taken over at least 2 d of treatment in 44 patients. The area under the concentration time curve (AUC) values normalized for a dose of 1 mg/kg were 7000 ng/ml x h on d 1 and 5890 ng/ml x h on d 4, thus showing a moderate decrease over time. This was accompanied by a moderate increase of the clearance from 2.6 to 3.0 ml/min/kg. Administration of busulphan as a DMSO-based intravenous formulation was well tolerated. The total dose of busulphan can be given in four (rather than the typical 16) doses. With such a regimen, the intravenous administration becomes feasible on an outpatient basis.     

Busulfan pharmacokinetics using a single daily high-dose regimen in children with acute leukemia

The pharmacokinetics of busulfan, given as a single daily dose (either 4 mg/kg or 150 mg/m2), was determined in 22 children undergoing bone marrow transplantation for acute leukemia. The single daily dose regimen showed similar pharmacokinetics to previously reported regimens of 4 x 1 mg/kg, except for fourfold higher mean peak plasma levels and negligible trough levels. Daily systemic exposure for single dose regimens based on weight (4 mg/kg) or surface area (150 mg/m2), respectively were very similar to regimens of (4 x 1 mg/kg) or (4 x 37.5 mg/m2). Dose (milligrams per kilogram), peak plasma level, and area under the curve (AUC) were all higher in 12 children treated with 150 mg/m2 busulfan than in 9 children treated with 4 mg/kg. AUC was age dependent for the 4 mg/kg dose but not for the 150 mg/m2 dose. The use of a 150 mg/m2 dose allows escalation of the dose above 4 mg/kg, eliminating the tendency for younger children to receive lower systemic exposure. Little toxicity was observed in this study. Clearance and distribution volume correlated negatively with age, and AUC correlated positively with dose (milligram per kilogram). Administration of busulfan as crushed rather than whole tablets reduced the delay time for appearance of busulfan in plasma but had no effect on absorption or other pharmacokinetic parameters.     

吡喹酮注射液在健康水牛体内的药物动力学

目的研究吡喹酮注射液在水牛体内的药物动力学特征及其与吡喹酮片之间的相对生物利用度。方法选用6头健康成年水牛,采用两周期随机交叉实验设计,单剂量内服吡喹酮片(20 mg/kg)或肌注吡喹酮注射液(10 mg/kg),高效液相色谱法(HPLC)测定水牛血浆中吡喹酮浓度,进行非房室模型分析,计算药动学参数。结果水牛内服吡喹酮片的峰时(T_(max))为(0.60±0.29)h,峰浓度(C_(max))为(0.57±0.37)μg/ml,消除半衰期(T_(1/2β))为(0.70±0.42)h,药-时曲线下面积(AUC)为(0.80±0.70)(μg/ml)·h。水牛肌注吡喹酮注射液的T_(max)为(0.65±0.49)h,C_(max)为(3.82±1.17)μg/ml,T_(1/2β)为(1.00±0.73)h,AUC为(1.61±0.89)(μg/ml)·h。吡喹酮注射液相对于吡喹酮片的生物利用度为402.5%。结论吡喹酮注射液肌注给药后在水牛体内具有吸收迅速,生物利用度高,体内分布广的药物动力学特征,临床推荐给药剂量为10 mg/kg。     

不同药物不同途径预防小鼠日本血吸虫感染的效果比较

目的　比较吡喹酮等药物不同途径预防小鼠日本血吸虫感染的效果。　方法　将吡喹酮、氯硝柳胺、丙硫咪唑和中药 W按一定剂量单独或配伍对小白鼠灌胃给药 ,进行 12 h预防日本血吸虫感染试验。同时进行含不同剂量不同透皮促进剂 (二甲亚砜、Azone、1,2 -丙二醇 )吡喹酮霜剂的小鼠 12 h或 2 4 h皮涂防护试验 ,并用环卵沉淀试验 (COPT)检测皮涂小鼠血清抗血吸虫抗体。　结果　皮涂各组减虫率均为 10 0 % ,可达 12 h或 2 4 h完全防护 ,透皮促进剂中 Azone用量少且无臭 ,COPT灵敏度和特异度均较高。灌胃各组比较 ,中药 W减虫效果明显 ,但毒性较大 ;吡喹酮单用及合用效果均好于氯硝柳胺 ,且吡喹酮与丙硫咪唑合用有一定增效作用 ,其中吡喹酮 14 0 m g/ kg合并丙硫咪唑 6 0 mg/ kg可达 12 h完全防护。　结论　皮涂吡喹酮霜剂效果好于口服预防 ,透皮剂中 Azone较理想 ,口服预防联合用药可降低剂量和毒性 ,提高防护效果。     

伊维菌素和阿苯达唑伍用治疗钩虫、鞭虫感染的疗效观察

目的　观察伊维菌素和阿苯达唑伍用驱治钩虫和鞭虫感染的疗效。　方法　用伊维菌素 6mg和 12mg分别伍用阿苯达唑 2 0 0mg顿服治疗钩虫感染者 ,伊维菌素 12mg伍用阿苯达唑 2 0 0mg顿服治疗鞭虫感染者 ;同时 ,用阿苯达唑40 0mg顿服分别治疗钩虫和鞭虫感染者。用虫卵阴转率评价疗效。　结果　 6mg和 12mg伊维菌素伍用阿苯达唑治疗钩虫感染者 ,其虫卵阴转率分别为 93 .3 %和 95 .5 % ,12mg伊维菌素伍用阿苯达唑治疗鞭虫感染者 ,其虫卵阴转率为 94.3 % ;而单用阿苯达唑治疗钩虫和鞭虫感染者 ,其虫卵阴转率分别为 66.7%和 47.1%。　结论　伊维菌素和阿苯达唑伍用驱治钩虫和鞭虫感染的效果良好 ,两药有协同作用 ,而不良反应轻微、短暂。     

三苯双脒、青蒿琥酯、蒿甲醚和吡喹酮单剂、多剂或联合用药治疗大鼠华支睾吸虫感染的实验研究

目的 观察三苯双脒、青蒿琥酯、蒿甲醚、或吡喹酮单剂、多剂给药,及其伍用治疗感染华支睾吸虫大鼠的疗效。 方法 147只SD大鼠各感染50个华支睾吸虫囊蚴,于感染后42～44 d分组治疗。各药物采用灌胃给药。①60只感染大鼠随机分为11组（每组4～5只）,分别为三苯双脒150 mg/kg（顿服）、75 mg/（kg·d）×2 d、50 mg/（kg·d）×3 d和25 mg/kg（tid）×2 d组;吡喹酮150 mg/kg（顿服）、75 mg/（kg·d）×2 d和25 mg/kg（tid）×2 d;青蒿琥酯或蒿甲醚75 mg/kg（顿服）和37.5 mg/（kg·d）×2 d组。②另87只感染大鼠随机分为15组（每组4～6只）,用青蒿琥酯或蒿甲醚（30 mg/kg）分别与吡喹酮（150 mg/kg）、三苯双脒（50 mg/kg和75 mg/kg）伍用组;三苯双脒（50 mg/kg）与吡喹酮（150 mg/kg）伍用组;三苯双脒（75 mg/kg）与吡喹酮（187.5 mg/kg）伍用组,及各药的单用组。并设同批感染未治疗对照组。受治鼠于治疗后2周剖杀,收集胆管和肝组织内的残留华支睾吸虫,计算各组的平均虫数和减虫率,用非参数统计方法（Mann-Whitney秩和检验）对相应组间的平均虫数进行分析。 结果 感染华支睾吸虫的大鼠口服单剂三苯双脒或吡喹酮（150 mg/kg）的减虫率分别为57.2%和63.8%。三苯双脒各小剂量多次给药组的减虫率稍高,达77.1%～79.4%,而吡喹酮小剂量多次给药组的减虫率则为50.6%～54.2%。但两种药物各组间的平均虫数的差异无统计学意义。青蒿琥酯和蒿甲醚各单剂给药组与小剂量多次给药组的减虫率均较高,分别为90.4%～98.5%和100%。三苯双脒小剂量（50或75 mg/kg）与吡喹酮（150 mg/kg 或187.5 mg/kg）伍用治疗,减虫率为74.9%～100%,高于其各单药组的减虫率（26.9%～79.6%）。青蒿琥酯或蒿甲醚小剂量（30 mg/kg）与吡喹酮（150 mg/kg）或三苯双脒（50或75 mg/kg）伍用治疗,减虫率为74.9%～97.9%,亦高于其各药组的减虫率（24.8%～79.6%）。 结论 青蒿琥酯、蒿甲醚、吡喹酮和三苯双脒均为有效的抗华支睾吸虫药物,各药物小剂量伍用具有增效作用。     

4种药物单用或联用治疗大鼠华支睾吸虫感染的实验研究

目的观察三苯双脒(TBD)、青蒿琥酯(AS)、阿苯达唑(ABZ)、甲苯咪唑(MBZ)单用或联用治疗感染华支睾吸虫大鼠的疗效。方法 140只大鼠各感染华支睾吸虫囊蚴100个,于感染后第5周开始分组治疗,均采用灌胃给药。感染大鼠随机分为药物治疗组同批感染对照组(每组5～10只),将TBD、AS、ABZ与MBZ分别按照高、低剂量单剂用药和两两配伍给药,顿服,观察疗效。治疗后10d处死大鼠,解剖,收集胆管和肝组织内的华支睾吸虫,计算平均虫数和减虫率,对相应组间的平均虫数进行单因素方差分析。结果感染华支睾吸虫大鼠用75mg/kg体重TBD、MBZ、ABZ单剂治疗后,平均减虫率分别为98.04%、100%和86.67%,30mg/kg体重AS治疗后减虫率为87.25%;当给药剂量均降低1/3时,上述各药物治疗组的平均减虫率分别降至78.3%、46.02%、31.94%和62.07%。50mg/kg体重TBD分别与50mg/kg体重MBZ、ABZ配伍用组平均减虫率为98.43%和100%,检虫数与75mg/kg体重TBD、MBZ、ABZ单用药组比较,差异有统计学意义(P<0.05)。20mg/kg体重AS分别与50mg/kg体重ABZ、50mg/kg体重MBZ配伍用,平均减虫率为89.22%和97.55%,检虫数与75mg/kg体重ABZ、MBZ,30mg/kg体重AS单用药组比较,差异有统计学意义(P<0.05)。结论联合用药可降低给药剂量,并具有增效作用,50mg/kg体重TBD分别与50mg/kg体重MBZ、ABI配伍用对治疗大鼠华支睾吸虫病疗效较好。     

Sequential analysis of helminth egg output in human stool samples following albendazole and praziquantel administration

Large-scale administration of anthelminthic drugs currently is the most widely used intervention for controlling morbidity due to schistosomiasis and soil-transmitted helminthiasis. An important issue is drug efficacy monitoring. However, the optimal time points post-treatment for assessing the efficacy of praziquantel against Schistosoma mansoni and albendazole against hookworm infections are not known. Forty-nine schoolchildren infected with S. mansoni and 52 infected with hookworm were treated with a single oral dose of praziquantel (40 mg/kg) and albendazole (400 mg), respectively. Stool samples were collected on 19 occasions over a 44-day post-treatment follow-up period, and two Kato-Katz thick smears per sample were examined at each time point. Both the mean egg counts and observed cure rates varied depending on the time point post-treatment. The highest reduction in the geometric mean egg counts (>97%) and the highest observed cure rate (>97%) of S. mansoni infections were found 15-20 days after praziquantel administration. Among the hookworm-infected children, egg counts decreased rapidly within the first week after albendazole administration (>95%), whereas infection rates showed high and heterogeneous (45.0-71.2%) levels at later time points. Both praziquantel and albendazole were highly efficacious in reducing the overall egg burden of S. mansoni and hookworm, respectively. We suggest that 15-20 days post-treatment is the most appropriate time point for efficacy evaluation of praziquantel against S. mansoni. Although no clear conclusion can be drawn for the optimal timing of efficacy evaluation of albendazole against hookworm, a 2-3-week time frame seems a reasonable compromise. This is justified on logistical grounds (i.e. collection of stool samples only once) and growing emphasis on integrating the control of schistosomiasis and soil-transmitted helminthiasis, including drug efficacy monitoring.     

Low efficacy of mebendazole against hookworm in Vietnam: two randomized controlled trials

Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010. The treatment used in Vietnam is single dose oral mebendazole (Phardazone) 500 mg. We tested the efficacy of single dose mebendazole 500 mg in the therapy of hookworm infection in a randomized double-blind placebo-controlled trial among 271 Vietnamese schoolchildren. The treatment efficacy of single dose mebendazole in children did not differ significantly from placebo, with a reduction in mean eggs per gram of feces relative to placebo of 31% (95% CI -9 to 56%, P = 0.1). In light of these findings we then carried out a similar randomized trial comparing triple dose mebendazole, single dose albendazole, and triple dose albendazole against placebo in 209 adults in the same area. The estimated reduction in mean post-treatment eggs per gram of feces relative to placebo was 63% (95% CI 30-81%) for triple mebendazole, 75% (47-88%) for single albendazole, and 88% (58-97%) for triple albendazole. Our results suggest that single dose oral mebendazole has low efficacy against hookworm infection in Vietnam, and that it should be replaced by albendazole. These findings are of major public health relevance given the opportunity costs of treating entire populations with ineffective therapies. We recommend that efficacy of anti-helminth therapies is pilot tested before implementation of national gut worm control programs.     

甲苯达唑、阿苯达唑及其代谢物实验治疗小鼠继发性细粒棘球蚴病的研究

在疗程为10～14d时,甲苯达唑对小鼠继发性细粒棘球蚴病的最低有效剂量为25mg/kg/d,阿苯达唑的为100mg/kg/d。在所用的疗程下,甲苯达唑的剂量较阿笨达唑100～300mg/kg/d低3～11倍时,它们的疗效相仿,但甲苯达唑100mg/kg/d的疗效则优于剂量大l～2倍的阿苯达唑。甲苯达唑与阿苯达唑合并治疗未能明显提高疗效,但此2种药物并用吡喹酮治疗则疗效明显提高。实验证明阿苯达 唑亚砜的疗效优于阿苯达唑,而阿苯达唑用则无效。     

日本血吸虫病与肠线虫病联合化疗的效果

血吸虫病人合并感染肠线虫者(A组)采取;吡喹酮40mg/kg加阿苯达唑200mg和复方甲苯咪唑400mg(尚含左旋咪唑100mg)分2d顿服,1个半月后血吸虫阴转率88.0％,蛔虫、鞭虫和钩虫阴转率分别为77.4％、23.6％及100.0％。对不合并血吸虫病的肠线虫病患者采取两种联合化疗方案:B组—阿苯达唑200mg和复方甲苯咪唑200mg(尚含左旋咪唑50mg)顿服,蛔虫、鞭虫和钩虫的阴转率分别为66.7％、18.8％和62.5％,较A组结果稍低;C组—阿苯达唑100mg和噻嘧啶900mg顿服的驱虫效果差,蛔虫和鞭虫的阴转率分别为50.0％及11.1％。3种驱虫方案对血吸虫和蛔虫的减卵率可达97.0％～99.9％;对钩虫的减卵率达68.9％～100％;对鞭虫的效果差。相应增加药物的剂量及改进服法,当可提高疗效。     

甲苯达唑、阿苯达唑和吡喹酮实验治疗小鼠继发性细粒棘球蚴病的观察

小鼠于感染继发性细粒棘球蚴后用甲苯达唑口服治疗,剂量为12.5～100mg/kg/d×10时囊肿抑制率为49.2～77.5％,用阿苯达唑100～300mg/kg/d×10～14治疗的为61.3～72.1％,而用吡喹酮400mg/kg/d,或800mg/kg/d,2次均服,疗程为10d时则无效,但若给服500mg/kg/d×14,囊肿抑制率为63.4％。药物有效各组的每鼠平均囊数,除个别组外,均较相应对照组的为少。此外,甲苯达唑与吡喹酮合并服用,有一定的增效作用。     

三苯双脒肠溶片治疗肠道线虫感染的效果观察

目的 观察三苯双脒（Tribendimidine)肠溶片对钩虫、蛔虫和蛲虫感染的驱虫效果和可能发生的不良反应。方法 对2岁以上单纯钩虫、蛔虫、蛲虫感染或混合感染者251例随机分组，比较成人服用单剂三苯双脒400mg或阿苯达唑400mg治疗钩虫感染和蛲虫感染，三苯双脒300mg或阿苯达唑400mg治疗蛔虫感染的驱虫效果及不良反应。结果 三苯双脒、阿苯达唑对蛔虫感染的虫卵阴转率分别为98．0％（49／50）和100．0％；对钩虫感染的虫卵阴转率分别为92．0％（46／50）和74．0％（37／50）；对蛲虫感染的虫卵阴转率分别为7／10和9／10。三苯双脒的不良反应发生率低而轻，对血象、肝肾功能和心电图无明显影响。结论 三苯双脒400mg治疗美洲钩虫和十二指肠钩虫感染有显著疗效，300mg组与阿苯达唑400mg组治疗蛔虫感染的效果相当，对蛲虫感染也有效，并且有排虫快，服药简便、不良反应少而轻等优点。     

Albendazole treatment for Giardia intestinalis infections in school children

A randomized controlled trial, 113 school children with Giardia intestinalis infection were treated with albendazole or tinidazole. Albendazole 400 mg once a day x 3 days and tinidazole 50 mg/kg single dose were given orally to 62 and 51 children, respectively. Parasitological cure was documented when there were > or = 2 times negative stool examination for G. intestinalis at 1-2 weeks after therapy. Thirty-one of 62 (50%) children treated with albendazole and 49 of 51 (96.1%) children treated with tinidazole had parasitological cure (p < 0.001). No major side effects were observed except one case in tinidazole group had severe headache for 30 hours. Albendazole appears to be safe and produced a moderate cure rate for G. intestinalis infection when a 3 day anthelmintic regimen is given.     

Single and multiple dose pharmacokinetics of rifapentine in man: part II.

OBJECTIVE: To characterize the pharmacokinetics of rifapentine following single, multiple, and intermittent doses. DESIGN: Twenty-three healthy male volunteers were randomized in a two-period, incomplete block, crossover design to receive two of four possible treatments: single daily oral rifapentine doses of 150, 300, or 600 mg given on day 1 and again on days 4-10, or a single oral 600 mg dose given on days 1, 4, 7, and 10. RESULTS: Maximum rifapentine plasma concentrations were observed in 4-5 hours. Mean rifapentine t(1/2) ranged from 13.2-14.1 hours and was similar across the 150-600 mg dose range. The changes in rifapentine Cmax (R = 0.86) and AUC(0-->infinity) (R + 0.90) were dose linear. The active 25-desacetyl metabolite appeared slowly in plasma, with mean Tmax of 14.4-17.8 hours. Mean t(1/2) for 25-desacetyl-rifapentine ranged from 13.3-24.3 hours. Disproportionate, dose-dependent increases in rifapentine and 25-desacetyl-rifapentine AUC were observed as single doses of rifapentine increased from 150 to 600 mg. At steady state, however, the magnitude of dose dependency was much less. CONCLUSION: Maximum plasma rifapentine concentrations were well above minimum inhibitory concentrations for Mycobacterium tuberculosis and M. avium following single 600 mg doses. In addition, the extended t(1/2) of rifapentine and its active metabolite support clinical investigation of once or twice-weekly rifapentine dosage regimens of rifapentine for the management of tuberculosis.