Plasma pharmacokinetics and tissue distribution of paclitaxel in CD 2 F 1 mice
Julie L. EisemanNatalie D. EddingtonJames LeslieClaudia MacAuleyDorothy L. SentzMichael ZuhowskiJacqueline M. KujawaDavid YoungMerrill J. Egorin
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Bolus (digestion)
Caco-2
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The absolute bioavailability of 8-methoxypsoralen in gelatin capsules and as a solution was studied in dogs. A dose of 2 mg kg-1 was given. Both for the solution and the gelatin capsules, a large variation in bioavailability was found between the different dogs. For the gelatin capsules in 1 dog out of 4 an absolute bioavailability of more than 100 per cent was found; for the solution a bioavailability of more than 100 per cent was found in all 4 dogs. Resorption was more rapid and bioavailability higher for the solution than for the gelatin capsules. Relative bioavailability of an emulsion and of a solution of 8-methoxypsoralen was studied in 2 dogs. A faster resorption and a higher bioavailability were found for the solution.
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Half-life
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Alfentanil
Bolus (digestion)
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瞄准：由于源于先进胃的癌症的腹膜炎 carcinomatosa 与腹水在病人在它的静脉内的管理以后在血浆和腹水检验 paclitaxel 集中。方法：有腹水的二个病人在这研究由于源于胃的癌症的腹膜炎 carcinomatosa 被包括。在血浆和腹水的 paclitaxel 集中为 72 h 被调查以防 1 和 168 h 以防 2 在静脉内的管理以后。结果：在血浆的 paclitaxel 集中在管理以后立即达到顶点，在 24 h 以内在 0.1 微摩尔(85 ng/mL ) 的阀值价值下面由快速的减少列在后面。相反，在腹水的 paclitaxel 集中在管理以后为 24 h 逐渐地增加了到与在血浆发现的水平一致的水平。在 24 h 以后，在腹水和血浆的 paclitaxel 的水平变得类似，与被维持直到 72 h 追随者管理的最佳的水平。结论：在腹水的 paclitaxel 的集中在静脉内的管理以后为多达 72 h 为癌症房间的治疗在最佳的水平以内被维持。Paclitaxel 是为胃的癌症的恶意的腹水的治疗的有希望的药。
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Crossover study
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This chapter contains sections titled: Introduction Oral Bioavailability Definition Cassette Dosing Across-species Prediction of Bioavailability In silico Models for Estimating Human Oral Bioavailability Quantitative Structure–Activity Relationship (QSAR) Approaches Molecular Properties Influencing Bioavailability Estimation of Bioavailability from Calculated Absorption ACE Inhibitors β-Blockers Calcium Antagonists In vitro Model for Predicting Oral Bioavailability in Human and other Species In vivo Method for Estimating Human Oral Bioavailability from Animal Pharmacokinetic Studies Factors to Consider in Optimizing Oral Bioavailability
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Studies have reported high prevalence of inappropriate dosing in patients with renal impairment, which was significantly reduced with pharmacists' interventions. The objective of this study was to assess the proportions of renal drug dosing errors following the implementation of pharmacists-led renal drug dosing adjustment program. This was a quasi-experimental study conducted at the King Abdul Aziz Medical City, a tertiary teaching hospital, Jeddah, Saudi Arabia. The study comprised of 3 phases. The pre-phase and post-phase evaluated drug orders for dosing appropriateness. During the intervention phase, a renal drug dosing adjustment program was implemented, which included educational sessions on dosing in renal insufficiency and a renal drug dosing guidance. The primary outcome was to assess the change in the proportions of dosing errors following the intervention. In the pre-phase, inappropriate dosing was noted in 20.1% (70/348) of orders that required dosing adjustment. Among the total dosing errors, 44.2% (31/70) were further corrected, and pharmacists have documented intervention in 48.3% (15/31) of the corrected orders. In the post-phase, inappropriate dosing was noted in 21.9% (76/346) of orders that required dosing adjustment. Among the total dosing errors, 39.4% (30/76) were further corrected, and pharmacists have documented intervention in 66.6% (20/30) of the corrected orders. There was no statistically significant difference in inappropriate drug dosing between pre-phase and post-phase with a P = 0.56. The intervention was not associated with significant reduction in renal dosing errors, although pharmacist involvement in the corrected orders orders increased after the implementation of the intervention. This may indicate the need to integrate renal dosing guidance into the hospital prescribing system to optimize drug dosing in renal patients.
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Paclitaxel, an effective antitumor agent, is formulated in various vehicles serving as carriers to deliver the hydrophobic paclitaxel to tissue. The approved formulations in the U.S. are paclitaxel formulated in Cremophor EL (currently known as Kolliphor EL) and nanoparticle albumin-bound paclitaxel (nab–paclitaxel). Despite having the same active ingredient (paclitaxel), different formulations produce distinct products with unique efficacy and safety profiles. A semimechanistic model was developed to describe the pharmacologic sensitivity of paclitaxel under different formulations. Circulating paclitaxel concentration data from patients treated with nab–paclitaxel or Cremophor EL–paclitaxel were analyzed in NONMEM using a semimechanistic model with simultaneous disposition of paclitaxel–carrier complexes and the total paclitaxel released from the complexes. The key factors driving paclitaxel exposure in circulation and peripheral tissues were explored via sensitivity analysis. The rapid decline of total paclitaxel concentration following intravenous administration of nab–paclitaxel and Cremophor EL–paclitaxel was attributed to rapid tissue distribution of the paclitaxel–carrier complexes, with minor contribution of free and protein-bound paclitaxel. Distribution of nab–paclitaxel to peripheral tissue was 4-fold faster and 10-fold more extensive than that of Cremophor EL–paclitaxel micelles, resulting in distinct tissue paclitaxel profiles. Sensitivity analyses showed the plasma paclitaxel–time profile was insensitive to the rapid rates of tissue distribution and decomposition of paclitaxel–carrier complexes but that the tissue distribution profile of paclitaxel was highly sensitive. Tissue distribution of paclitaxel is carrier complex system-dependent. Different delivery systems result in distinct tissue paclitaxel profiles but similar paclitaxel concentration–time profiles in plasma or blood, rendering the paclitaxel plasma profile a poor surrogate for its clinical outcome.
Taxane
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Pharmacokinetics of paclitaxel in a hemodialysis patient with advanced gastric cancer： A case report
我们第一次为一个病人报导每周的 paclitaxel 化疗的可能性与先进， nonresectable 胃的癌症经历牙齿过敏细胞溶解。有长期的肾衰竭的一个 50 岁的人由于双边的 polycystic，一个星期经历牙齿过敏细胞溶解三次 5 年了，在 2004 年 12 月与吐血介绍了。与淋巴节点转移基于胃的癌症的诊断，外科被执行。在第 15 手术后的天，病人用 paclitaxel 与化疗被对待。Paclitaxel 在 saline 的 250 mL 作为 1 h iv 注入在 60 mg/m2 的剂量被管理。血液透析被开始在 paclitaxel 注入的结束以后的 1 h 并且为 3 h 被执行。Paclitaxel 在 d 上每周被管理 1， 8，和 15 在 28-d 上骑车。paclitaxel 的最大的血浆集中是 1390 microg/L。在 paclitaxel 的曲线下面的区域是 4398.6 microg x h/L。等级 2 白细胞减少在第一个周期期间被遇到。到在注入以后的超过 24 h 的从 6 的 paclitaxel 的血浆集中是在我们的病人的 0.01 ～ 0.1 micromol/L，并且这些集中被显示了在没有在病人生产不利副作用，禁止胃的癌症房间的生长上有效。paclitaxel 的血浆集中没被牙齿过敏细胞溶解影响。我们断定 paclitaxel 的 pharmacokinetics 没与肾衰竭在一个病人被改变，并且那每周的 paclitaxel 是为有先进胃的癌症的牙齿过敏细胞溶解病人的合适的治疗政体。
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