Maximal tolerated dose

The drug should be administered at three levels by the route proposed for humans. The high dose level should be set so as to have relevance in humans. For drugs that display significant toxic effects, this may be related to the maximally tolerated dose in the toxicity tests, for example, the dose causing less than 10% deviation in body weight versus controls. If there is little evidence of toxicity it may be more appropriate to base the dose level on a multiple (usually 25-fold) of the maximum therapeutic dosage recommended in humans. 

Is the patient at goal or maximally tolerated doses of vasodilator and P-blocker therapy ... 

Treatment should begin as early as possible in patients with a diagnosis of AD.30 Figure 32-2 provides a recommended treatment algorithm for AD.31 Patients should be switched to another ChE inhibitor from their initial ChE inhibitor if they show an initial lack of efficacy initially respond to treatment, but lose clinical benefit or experience safety/tolerability issues. This switch should not be attempted until the patient has been on a maximally tolerated dose for a period of 3 to 6 months. The switch should also be based on realistic expectations of the patient and/or caregiver.32 ChE inhibitor therapy should be discontinued in patients who experience poor tolerance or compliance, who show a lack of clinical improvement after 3 to 6 months at optimal dosing, who continue to deteriorate at the pretreatment rate, or who demonstrate dramatic clinical deterioration following initiation of treatment.33... 

Doses should be doubled no more often than every 2 weeks, as tolerated, until the target dose or the maximally tolerated dose is reached. Patients... 

In the absence of target organ toxicity with which to set the high dose at the maximally tolerated dose, the high dose can be set at the dose that produces an area under the curve (AUC). This is 25-fold higher than that obtained in human subjects. 

A ratio that characterizes the relative effectiveness of a pharmaceutical. It is equal to the maximally tolerated dose divided by the minimal curative or effective dose or, to LD50/ED50. 

In a study of carcinogenesis, DBCP was orally administered to rats and mice 5 times/week at maximally tolerated doses and at half those doses. ° As early as 10 weeks after initiation of treatment, there was a high incidence of squamous cell carcinomas of the stomach in both species. In female rats there were also mammary adenocarcinomas. Chronic inhalation resulted in carcinomas of the respiratory tract in mice and multiple site tumors in rats. ... 

TEL is not an irritant, and no unpleasant sensations are related to skin contact or inhalation. The ability to penetrate skin makes reliance on airborne concentrations impractical. Teratogenic effects have not been observed after exposure to maximally tolerated doses in mice or rats. Rodent embryos may serve as a poor model for human femses because the hepatic microsomal metabolizing... 

PR) and median survival was 26 mo. The 3-yr survival probability is 0.47 (64). Because dose escalation was limited to 74 Gy without reaching a maximally tolerated dose, a further trial is underway to find the true MTD of dose-escalated thoracic radiation with concurrent carboplatin-paclitaxel-based chemotherapy. 

Regional block, a form of anesthesia that includes spinal and epidural anesthesia, involves injection near a nerve or nerve plexus proximal to the surgical site. It provides excellent anesthesia for a variety of procedures. Brachial plexus block is commonly used for the upper extremity. Individual blocks of the sciatic, femoral, and obturator nerves can be used for the lower extremity. An amount that is close to the maximally tolerated dose is required to produce blockade of a major extremity. 

The National Toxicology Program performed a subchronic study of CN to generate data on the maximally tolerated dose (MTD) of this agent preparatory to launching a full-scale chronic-toxicity and carcinogenicity bioassay.38 The test was conducted in Fischer 344... 

B. Indications and use Sandostatin is indicated to reduce blood levels of growth hormone and IGF-I (somatomedin-C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, or bromocriptine mesylate at maximally tolerated doses. It is also indicated for the symptomatic treatment of patients with metastatic carcinoid tumors, where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease, and for the treatment of the profuse watery diarrhea associated with VIP (vasoactive intestinal peptide)-secreting tumors (vipomas). 

The low response of cancer patients to LPS treatments may be due to low maximal tolerated dose (MTD), 4 ng/kg. In order to avoid this problem, several trials were performed with lipids A. 

Several lipids A have been tested in cancer patients MPLA, SDZ MRL 953, and ONO-4007 were injected i.v. in phase I trials. The maximal tolerated dose found is lower than or close to the optimal dose defined in animals. Humans are more sensitive to lipid A than rodents so it is possible that similarly to the toxic dose, the effective dose is lower in humans than in animals. 

The triazine herbicides, with the exception of cyanazine, did not produce developmental or reproductive effects at maximally tolerated doses. Cyanazine produced developmental effects in rats and rabbits at the highest doses tested. Effects noted at doses that were toxic to the mothers were cyclopia and diaphragmatic hernia in rabbits and an apparent increase in the incidence of skeletal variations (i.e., anomalies) in rats (USEPA, 1994). 

Melphalan induced cancer at the site of injection (peritoneal cavity) in mice and rats given three injections per week at the maximally tolerated dose [94]. 

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