Single-dose therapeutic

Proof-of-concept studies have demonstrated that lOOx Cmax is a reasonable scaling factor to differentiate hepatotoxic (or positive) versus nontoxic (or negative) drugs.108 For example, in a family of antidepressant drugs, nefazodone was consistently positive, whereas buspirone and fluoxetine remained negative, but all tested at 100x of their respective single-dose therapeutic Cmax.108... 

If possible, these developability pharmacology studies should be conducted with dosing to steady state unless the frequency of dosing to be used in clinical trials is as a single-dose therapeutic. The number of doses required to reach steady state depends on the lead s pharmacokinetic profile in the same animal model. These multiple-dose studies provide information on the frequency of dosing necessary to maximize the biological response. This is particularly important for compounds that inhibit an enzymatic system or are effective only during certain phases of the cell cycle. 

The single dose of a drug is mo.stly derived from experience it is only possible in a very few cases to calculate it from the activity of the constituents. However, as many herbal drugs arc only weakly active and contain non-toxic substances, i.e, the therapeutic index is large, exceeding the dose is usually only of minor significance nevertheless, the pharmacist must know what the exceptions are in this book, the sections on Side effects and Making the tea draw particular attention to such cases, c.g. arnica flowers, liquorice root, etc. 

Usually, one has obtained an estimate for the elimination constant and the distribution volume Vp from a single intravenous injection. These pharmacokinetic parameters, together with the interval between administrations 0 and the single-dose D, then allow us to compute the steady-state peak and trough values. The criterion for an optimal dose regimen depends on the minimum therapeutic concentration (which must be exceeded by and on the maximum safe... 

In view of bcl-2 s major neuroprotective and neurotrophic roles, a study was undertaken to determine if lithium, administered at therapeutically relevant concentrations, affects neurogenesis in the adult rodent brain. To investigate the effects of chronic lithium on neurogenesis, mice were treated with therapeutic lithium (plasma levels 0.97 0.20 mM), for 4 weeks. After treatment with lithium for 14 days, the mice were administered single doses of BrdU (bromodeoxyuridine, a thymidine analog which is incorporated into the DNA of dividing cells) for 12 consecutive days. Lithium treatment continued throughout the duration of the... 

Results clearly indicated effects of diesel exhausts from different engine operating conditions on the cells already after 1 h of exposure. However, a 1-h continuous exposure to a therapeutic aerosol is probably of limited clinical relevance. To study the effect of drugs administered by typical pharmaceutical single-dose inhalers (MDI, DPI) effective deposition of one puff within the time of one breathing maneuver ( 5 s) is probably more relevant. 

Population PK analysis following a single dose of 30 mg microencapsulated octreotide acetate intramuscularly the PK profile of microencapsulated octreotide acetate was effectively described by the derived population model. The relationship between IGF-1 and drug concentration could be used to guide optimization of therapeutic octreotide dosage regimens... 

Some psychiatric medications also produce a response within minutes of taking a single dose. Their therapeutic benefit can come very quickly. For example, taking a benzodiazepine such as diazepam (Valium) can quickly relieve panic and anxiety. Taking a stimulant can often rapidly relieve the symptoms of attention deficit-hyperactivity disorder (ADHD). When psychiatric medications work this quickly, we assume that the therapeutic benefit is a direct consequence of their initiating action in the synapse. 

In contrast to the limited value of pharmacokinetics to the use of antidepressants, knowledge of the kinetics of lithium has been important in defining the therapeutic and toxic range in unipolar or bipolar manic patients. Prediction of the dose required by the individual patient by giving a single dose of the drug and measuring the erythrocyte/plasma lithium... 

Rnally, pharmacokinetic and pharmacokinetic/pharmacodynamic modelling can be used for the purpose of prediction of the concentration-time profile of the drug and drug-carrier conjugate after repeated administration from single dose data, as well as for the prediction of the dose needed to maintain the concentration at the target site within a therapeutic window. 

A single dose of liothyronine administered IV produces a detectable metabolic response in as little as 2 to 4 hours and a maximum therapeutic response within 2 days. 

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