WordNet

travel or traverse (a distance); "This car does 150 miles per hour"; "We did 6 miles on our hike every day"
the syllable naming the first (tonic) note of any major scale in solmization (同)doh, ut
proceed or get along; "How is she doing in her new job?"; "How are you making out in graduate school?"; "Hes come a long way" (同)fare, make_out, come, get along
create or design, often in a certain way; "Do my room in blue"; "I did this piece in wood to express my love for the forest" (同)make
carry on or function; "We could do with a little more help around here" (同)manage
get (something) done; "I did my job" (同)perform
treat with an agent; add (an agent) to; "The ray dosed the paint"
the quantity of an active agent (substance or radiation) taken in or absorbed at any one time (同)dosage
a measured portion of medicine taken at any one time (同)dosage
relating to or involved in therapy; "therapeutic approach to criminality" (同)therapeutical
branch of medicine concerned with the treatment of disease
treated with some kind of application; "a mustache dosed with bear grease"

PrepTutorEJDIC

〈C〉《通例a~》1回分の投薬量 / 〈U〉《まれ》投薬
《疑問文・否定文を作る》 / 《否定命令文を作る》 / 《助動詞とbe動詞のどちらも含まない文に用いて付加疑問を作る》 / 《強意語として》 / 《文》《助動詞とbe動詞のどちらも含まない文に用いて倒置文を作る》 / 《あいづちを打つ場合に》 / 《先行する動詞またはそれを含む述部の代用》 / 《so,nor,neitherで始まる簡略文で》 / …‘を'『する』,行う,果たす / 《通例have done,時にbe doneの形で》…‘を'『終える』,済ませる / …‘を'作る,作り出す / …‘を'『処理する』,整える,片付ける / 〈学課〉‘を'『勉強する』,専攻する / 〈利益・害など〉‘を'与える,もたらす / 〈人〉‘に'『役立つ』,用が足りる(serve) / …の速度で進む,距離を行く / …‘を'見物する / 〈劇〉‘を'上演する;…‘の'役を演じる / …の役目(仕事)をする / 《おもに英》…‘を'だます,かつぐ / 《話》…をへとへとにさせる / 『する』;活動する / 《通例have done,時にbe doneの形で》(…を)『終える』,済ます《+『with』+『名』》 / 〈事が〉『運ぶ』;〈人が〉暮らしていく,健康である / 〈物が〉(…に)『間に合う』,十分である;〈人が〉(…に)役に立つ,向く《+『for』+『名』》 / 《複数形で》すべきこと / 〈C〉《おもに英》大宴会,大パーティー / 〈C〉《英話》詐欺,ぺてん
ド(全音階の第1音)
(おもに飲み薬1回分の)『服用量』 / (痛いこと・いやなことの)1回分,一定量 / (人などが受ける放射線の)線量 / 性病 / (…を)…‘に'投薬する,服用させる《+『名』+『with』+『名』》
治療[上]の
治療学

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/12/06 09:04:08」(JST)

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[Wiki en表示]

The therapeutic index (also known as therapeutic ratio) is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death (in animal studies) or toxicity (in human studies).^[1]

Quantitatively, it is the ratio given by the lethal or toxic dose divided by the therapeutic dose.

In animal studies, the therapeutic index is the lethal dose of a drug for 50% of the population (LD₅₀) divided by the minimum effective dose for 50% of the population (ED₅₀).

Lethality is not determined in human clinical trials; instead, the dose that produces a toxicity in 50% of the population (TD₅₀) is used to calculate the therapeutic index.

While the lethal dose is important to determine in animal studies, there are usually severe toxicities that occur at sublethal doses in humans, and these toxicities often limit the maximum dose of a drug. A higher therapeutic index is preferable to a lower one: a patient would have to take a much higher dose of such a drug to reach the lethal/toxic threshold than the dose taken to elicit the therapeutic effect.

in animal studies, or for humans,

Generally, a drug or other therapeutic agent with a narrow therapeutic range (i.e. having little difference between toxic and therapeutic doses) may have its dosage adjusted according to measurements of the actual blood levels achieved in the person taking it. This may be achieved through therapeutic drug monitoring (TDM) protocols.

The therapeutic index varies widely among substances: most forgiving among the opioid analgesics is remifentanyl, which offers a therapeutic index of 33,000:1; tetrahydrocannabinol, a sedative and analgesic of herbal origin (genus Cannabis), has a safe therapeutic index of 1000:1, while diazepam, a benzodiazepine sedative-hypnotic and skeletal muscle relaxant has a less-forgiving index of 100:1 and morphine, a sedative, antidepressant, and analgesic also of herbal origin (genus Papaver) has an index of 70:1^[2] (which, however, is still considered very safe).

Less safe are cocaine, a stimulant and local anaesthetic; ethanol, a widely available sedative consumed world-wide: the therapeutic indices for these substances are 15:1 and 10:1 respectively. Even less-safe are drugs such as digoxin, a cardiac glycoside; its therapeutic index is approximately 2:1.^[3] Other examples of drugs with a narrow therapeutic range, which may require drug monitoring both to achieve therapeutic levels and to minimize toxicity, include: dimercaprol, theophylline, warfarin and lithium carbonate. Some antibiotics require monitoring to balance efficacy with minimizing adverse effects, including: gentamicin, vancomycin, amphotericin B (nicknamed 'amphoterrible' for this very reason), and polymyxin B.

The effective therapeutic index can be affected by targeting, in which the therapeutic agent is concentrated in its area of effect. For example, in radiation therapy for cancerous tumors, shaping the radiation beam precisely to the profile of a tumor in the "beam's eye view" can increase the delivered dose without increasing toxic effects, though such shaping might not change the therapeutic index. Similarly, chemotherapy or radiotherapy with infused or injected agents can be made more efficacious by attaching the agent to an oncophilic substance, as is done in peptide receptor radionuclide therapy for neuroendocrine tumors and in chemoembolization or radioactive microspheres therapy for liver tumors and metastases. This concentrates the agent in the targeted tissues and lowers its concentration in others, increasing efficacy and lowering toxicity.

Sometimes the term safety ratio is used instead, particularly when referring to psychoactive drugs used for non-therapeutic (e.g. nonmedical) purposes.^[4] In such cases, the "effective" dose is the amount and frequency that produces the desired effect, which can vary, and can be greater or less than the therapeutically effective dose.

The concept of safety ratio/TI also ignores the ease or difficulty of reaching a toxic or lethal dose. This is more of a consideration for recreational drug users. While heroin and common alcohol may appear similarly dangerous based on their safety ratio (6 vs 10), an inexperienced drinker most likely vomits and falls asleep long before ingesting life-threatening amounts of alcohol. On the other hand, heroin users are at a much greater risk of death from a misjudged dose due to varying drug purity, individual tolerances, and influence-affected judgment.

Protective index is a similar concept, except that it uses TD₅₀ (median toxic dose) in place of LD₅₀. For many substances, toxic effects can occur at levels far below those needed to cause death, and thus the protective index (if toxicity is properly specified) is often more informative about a substance's relative safety. Nevertheless, the therapeutic index is still useful as it can be considered an upper bound for the protective index, and the former also has the advantages of objectivity and easier comprehension.

References

^ Katzung and Trevor's Pharmacology Examination & Board Review; 9th edition; A.J.Trevor, B.G. Katzung, S.B.Masters, McGraw Hill, 2010, p. 15.
^ Stanley, Theodore H (2000). "Anesthesia for the 21st century". Proc (Bayl Univ Med Cent) 13 (1): 7–10. PMC 1821133. PMID 16389318. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1821133/.
^ Becker, Daniel E (2007 Spring). "Drug Therapy in Dental Practice: General Principles Part 2—Pharmacodynamic Considerations". Anesth Prog. 54 (1): 19–24. doi:10.2344/0003-3006(2007)54[19:DTIDPG]2.0.CO;2. ISSN 0003-3006. PMC 1821133. PMID 17352523. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1821133/.
^ Gable,, Robert S (2004). "Comparison of acute lethal toxicity of commonly abused psychoactive substances" (PDF). Addiction (99): 686–696. doi:10.1111/j.1360-0443.2004.00744.x. PMID 15139867. http://web.cgu.edu/faculty/gabler/toxicity%20Addiction%20offprint.pdf.

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English Journal

Topical photodynamic therapy of actinic keratoses with 5-aminolevulinic acid: Randomized controlled trial with six months follow-up.

Buinauskaite E, Maciulaitis R, Buinauskiene J, Valiukeviciene S.Author information Department of Skin and Venereal Diseases .AbstractAbstract Background: Topical 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) with some transient adverse events. Objective: The purpose of the study was to evaluate the efficacy and side effects of two different light doses when treating AKs with ALA-PDT on the face/scalp. Methods: Thirty-eight patients with two histologically confirmed AKs were enrolled in the within-patient comparison study. ALA-PDT was performed twice with two weeks interval for each AK. Patients were randomized to receive a light dose of 70 or 100 J/cm(2) as their first split face/scalp treatment. Follow-up examinations were carried out at months 3 and 6. Efficacy end point included clinical/histological AK clearance rate. Results: No significant difference in therapeutic efficacy and adverse events of ALA-PDT was found between the two light doses at both follow-up visits. At months 3 and 6 after PDT the rate of complete remission were respectively 100% and 92.1% for 70 J/cm(2), 92.1% and 84.2% for 100 J/cm(2). The adverse events of the treatment were rosacea 5/76 (6.58%), hyperpigmentation 4/76 (5.26%), hypopigmentation 4/76 (5.26%), transient milia 3/76 (3.95%). Conclusions: The topical ALA-PDT with the red light dose of 70 J/cm(2) is an effective treatment for mild and moderate AKs on the face/scalp with expected adverse events of pigmentation changes, rosacea and transient milia.
The Journal of dermatological treatment.J Dermatolog Treat.2014 Dec;25(6):519-22. doi: 10.3109/09546634.2013.848257. Epub 2013 Nov 12.
Abstract Background: Topical 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) with some transient adverse events. Objective: The purpose of the study was to evaluate the efficacy and side effects of two different light doses when treating AK
PMID 24215475

Adverse events associated with botulinum toxin injection: a multidepartment, retrospective study of 5310 treatments administered to 1819 patients.

Kim BW, Park GH, Yun WJ, Rho NK, Jang KA, Won CH, Chang SE, Chung SJ, Lee MW.Author information Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine , Seoul , Korea.AbstractBACKGROUND: The injection of botulinum toxin is now commonly used for many therapeutic and cosmetic purposes but because of its increased use more adverse events are being reported.
The Journal of dermatological treatment.J Dermatolog Treat.2014 Aug;25(4):331-6. doi: 10.3109/09546634.2013.789473. Epub 2013 Apr 24.
BACKGROUND: The injection of botulinum toxin is now commonly used for many therapeutic and cosmetic purposes but because of its increased use more adverse events are being reported.OBJECTIVE: To retrospectively evaluate and analyze the safety of botulinum toxin injections in terms of purpose and the
PMID 23537074

Anatomical specificity in the modulation of activity-regulated genes after acute or chronic lurasidone treatment.

Luoni A1, Rocha FF1, Riva MA2.Author information 1Department of Pharmacological and Biomolecular Sciences, University of Milan, I-20133 Milan, Italy.2Department of Pharmacological and Biomolecular Sciences, University of Milan, I-20133 Milan, Italy; Center of Excellence on Neurodegenerative Diseases, University of Milan, I-20133 Milan, Italy. Electronic address: M.Riva@unimi.it.AbstractLurasidone is a novel second generation antipsychotic drug characterized by a multi-receptor profile. Besides the high affinity for 5-HT2A and D2 receptors, it is also characterized by potent 5-HT7 receptor antagonism, which may be beneficial for mood and cognition. Considering that dose-dependent changes in receptor occupancy may differentially impact gene transcription, we aimed at investigating the effects of acute and chronic treatments with different doses of lurasidone (1, 3 and 10mg/kg) in rats on the expression of the activity-regulated genes Arc, Zif268 and Npas4, which are markers of neuronal activation and are also associated with neuroadaptive mechanisms. Our results show dose-dependent and anatomically-selective differences after acute and chronic lurasidone treatment. Indeed, the effects produced by acute treatment seem to reflect the modulatory activity of lurasidone at selected neurotransmitter receptors. In fact, low doses of the drug acted in the hippocampus, while high doses acted in the striatum, reflecting the high predominance of D2 receptor expression in this brain region. On the contrary, chronic treatment with lurasidone revealed a different profile of IEGs modulation, possibly reflecting neuroadaptive changes set in motion in response to repetitive drug exposure. In summary, the multi-receptor profile of lurasidone leads to the recruitment of different brain structures in a dose-related manner and this may be important for its therapeutic properties, particularly with respect to antidepressant activity and cognition.
Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2014 Apr 3;50:94-101. doi: 10.1016/j.pnpbp.2013.12.008. Epub 2013 Dec 18.
Lurasidone is a novel second generation antipsychotic drug characterized by a multi-receptor profile. Besides the high affinity for 5-HT2A and D2 receptors, it is also characterized by potent 5-HT7 receptor antagonism, which may be beneficial for mood and cognition. Considering that dose-dependent c
PMID 24361635

Japanese Journal

Developing Population Pharmacokinetic Parameters for High-Dose Methotrexate Therapy : Implication of Correlations among Developed Parameters for Individual Parameter Estimation Using the Bayesian Least-Squares Method

Watanabe Masahiro,Fukuoka Noriyasu,Takeuchi Toshiki [他]
Biological & pharmaceutical bulletin 37(6), 916-921, 2014-06
NAID 40020073520

第79回東京女子医科大学学会総会シンポジウム「放射線治療の最近の進歩」(1)原発性悪性脳腫瘍

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原発性脳腫瘍は悪性であっても中枢神経系外に転移することはまれである。また、悪性では境界が不明瞭で、十分な全摘をするのは困難である。さらに、脳内には血液脳関門が存在するため、化学療法薬剤の病変へ到達が十分ではなく、体幹部病変よりも効果が劣るのが一般的である。これらのことから、体幹部悪性腫瘍と比べ、原発性悪性脳腫瘍の治療には、局所治療である放射線治療の役割は大きく、どのようなタイミングで、どのような範 …
NAID 110009770441

Hepatocyte growth factor enhances the barrier function in primary cultures of rat brain microvascular endothelial cells

Yamada Narumi,Nakagawa Shinsuke,Horai Shoji,Tanaka Kunihiko,Deli Maria A.,Yatsuhashi Hiroshi,Niwa Masami
Microvascular Research 92, 41-49, 2014-03
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NAID 120005460337