During epilepsy treatment, a number of questions may arise regarding the administration of tau. These questions are related to the mechanisms by which tau contributes to the development of epilepsy, bioavailability of tau, steady-state peaks and troughs, and contraindications.
Using an IV bolus and then continuing to IV infusion to maintain a steady plasma concentration is an important technique in pharmacotherapy. The concept is based on the fact that drugs are distributed through the circulatory system to all tissues.
The overall rate of change in the drug level is the function of the rate of drug absorption and the rate of drug elimination. The rate of elimination is usually higher than the rate of absorption.
When a drug is administered via a single IV bolus, it is given at a very fast rate. This may cause discomfort, but it also provides a quick onset of therapeutic action. When a drug is given slowly over a period of time, it provides a slower onset of action, but it also provides minimal discomfort.
The bioavailability of a dose is a concept that may be determined by analyzing the clinical response of a drug. This can be achieved from plasma data, urine data, or the results of an acute clinical trial.
Steady-state peaks and troughs
During a steady-state dosing interval, plasma concentrations tend to fluctuate between peak and trough levels. The relationship between peak and trough concentrations can be easily calculated using an equation.
The equation can be applied to any dosing interval and provides a clear idea of how much of the drug remains in the body. The peak concentration is the highest concentration achieved at steady state. In the case of intravenous dosing, the peak concentration is usually the same as the steady state concentration. In the case of oral dosing, the peak concentration is much lower.
A typical steady-state peak concentration is about twice as high as the peak concentration achieved after a single dose. In this example, the average steady-state concentration is about 1 mg/L. The peak concentration is accompanied by a trough of about 8.8 mg/L. The trough is the lowest concentration achieved during a steady-state dosing interval.
A peak to trough ratio is an important measure to evaluate the effectiveness of a drug. This ratio is related to the trough-to-peak ratio, which is the concentration of a drug versus time.
Mechanisms by which tau contributes to epilepsy
Several mechanisms by which tau contributes to epilepsy have been identified. These include activation of phosphatase activity, the inhibition of tensin homolog deleted chromosome 10, and upstream kinases. Interestingly, the inhibition of phosphatase activity is considered a homeostatic response that may stabilize aberrant hyperexcitability. Moreover, a global reduction of tau may prevent the development of epilepsy.
In addition to its role in epilepsy, tau may mediate cognitive impairment in other diseases. Tau hyperphosphorylation is a symptom of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease.
In the temporal lobe, tau phosphorylation increases after kindling, a common occurrence in epilepsy. Similarly, tau phosphatase dephosphorylation reduces neuronal toxicity. In a fantastic article on how to hormone therapy clinic , we used whole-cell patch-clamp electrophysiology to assess the role of tau in neuronal excitability in vivo.
Several studies have shown that tau hyperphosphorylation in vivo contributes to cognitive impairment and disease-related cognitive deficits in patients with epilepsy. Moreover, tau hyperphosphorylation has been found to contribute to the development of dementia in patients with Alzheimer’s disease.
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