Dose selection and administration

To minimize the risk of induced arrhythmia, patients initiated or reinitiated on Betapace or Betapace AF should be placed for a minimum of 3 days (on their maintenance dose) in a facility that can provide cardiac resuscitation, continuous electrocardiographic monitoring, and calculations of creatinine clearance. For detailed instructions regarding dose selection and special cautions for people with renal impairment, see Administration and Dosage. 

Chlorpyrifos lethality to selected birds and mammals via single oral dose route of administration... 

Table 14.5 Chlorpyrifos Lethality to Selected Birds and Mammals via Single Oral Dose Route of Administration (Values are in mg chlorpyrifos/kg body weight lethal to 50% within 14 days.)...

The search for more potent, selective and safe PPARa agonists has been challenging and only a limited number of compounds have progressed into the clinic. A number of phenoxyacetic acid derivatives and other diverse structures have emerged recently. Oral administration of LY-518674 (6) produced a 208% elevation in HDL and a 96% decrease in serum TG in apoA-I transgenic mice [38,39]. Recent clinical studies with compound 6 revealed a decrease in TG and an increase in HDL similar to fenofibrate. However, compound 6 also raised LDL-C in a dose-dependent fashion, and to a much higher level than seen with fenofibrate [28]. Both agents also raised serum creatinine levels above the upper limits of normal in 35-38% of patients [28]. 

Metabolism and/or pharmacokinetic data, when available, should also be considered in the dose selection process. It is desirable that a drug not be administered at such a high dose that it is excreted in a different manner than at lower doses, such as the MRHD. Similarly, the high dose should not lead to the formation of metabolites other than those formed at lower (clinical) doses. If data show that a given dosage produces maximum plasma levels, administration of higher... 

Doses selected for safety pharmacology studies are typically based on the criteria established in the ICH S7A guidance.25 Doses should exceed those projected for clinical efficacy and at the upper limit be bound by (1) adverse pharmacodynamic effects in the safety pharmacology study (2) moderately adverse effects in other non-clinical studies that follow a similar route and duration of dosing or (3) limit of solubility/toxicity. In the absence of adverse effects, the maximum administrable dose can be used. If nonreusable animals enter the study, then the maximum tolerated dose may be appropriate. Most importantly, the doses/concentrations should establish the dose/concentration-response relationship of the adverse effect. 

Elderly Because elderly patients are more likely to have decreased renal function, take care in dose selection it may be useful to monitor renal function (see Precautions. Administration and Dosaoel. 

Safe and effective use Safe and effective use of botulinum toxin type A depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques. Physicians administering botulinum toxin type A must understand the relevant neuromuscular or orbital anatomy of the area involved and any alterations to the anatomy caused by prior surgical procedures. An understanding of standard electromyographic techniques is also required for treatment of strabismus and may be useful for the treatment of CD. 

Once the target is selected and agreed, the project team needs to explore requirements for the specific disease area medical need versus possible adverse effects, preferred dosing regimen, route of administration and target patient population. 

The test substance or vehicle is usually administered orally by intubation. If another route of administration is used, the tester should provide justification and reasoning for its selection, and appropriate modifications may be necessary. .. The dose to each animal should normally be based on the most recent individual body weight determination. However, caution should be exercised when adjusting the dose during the last trimester of pregnancy. Existing data should be used for dose selection to prevent excess maternal toxicity. 

It is relatively selective inhibitor of peak III cyclic AMP phosphodiesterase isoenzyme in cardiac and vascular muscle. In patients with CHF, it produces dose related and plasma concentration related increase in the maximum rate of increase of left ventricular pressure. Milrinone has a direct inotropic and direct arterial vasodilator activity. It is administrated by IV infusion 0.50 mg/kg over 10 min with a maximum daily dose of 1.13 mg/kg. 

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