CIRCADIAN CHANGES IN DRUG DISTRIBUTION:

Many factors may influence drug protein binding, these are: temperature, pH, physio-chemical-properties of the drug and plasma concentrations of the protein. Each of these factors could theorically be subject to temporal variations

Circadian variation in the drug protein binding of acidic and basic drugs have been reported both in human and animal studies .

Temporal variations in free plasma concentrations have been documented for anticonvulgant drugs, such as carbamazepine, diazepam, phyentoin and valproic acid, and for antineoplastic drug such as cirplatin. These changes are usually reported to be dependent on temporal variation in plasma protein levels, which are circadian-time dependent.

Temporal variations in plasma drug binding may have clinical implications only for drugs that are characterized by a high protein binding ( > 80 % ) and a small apparent Vd. Nevertheless the clinical consequences of circadian variations in plasma protein levels have not yet been demonstrated.

Circadian rhythms in membrane permeability have been cited for many years as a candidate mechanism for the governing of biological clocks . However, only a few studies have been devoted to circadian changes in membrane permeability to drugs.