Alora is a transdermal system designed to deliver estradiol

Alora is a transdermal system designed to deliver estradiol continuously and consistently over a 3-4 day period when placed on the skin. Alora provides systemic estrogen replacement theory in postmenopausal women. For a 36 cm^2 patch, the release rate of the drug is 0.1 mg of estradiol per day. Clinical trials have provided the following pharmacokinetic data. In one study, following applications of the patch, the peak concentration of the estradiol was found to be 144 pg mL^-1 (10^12 pg = 1 g) and the half life of estradiol was found to be 1 h. Over an 84 h dosing interval, the plasma clearance for estradiol from the Alora patch was found to be 61 L h^-1. What is the apparent volume of distribution in liters?

Solution

Pharmacokinetics

The skin metabolizes estradiol only to a small extent. On the contrary, orally administered estradiol is rapidly metabolized by the liver to estrone and its conjugates. It gives rise to higher circulating levels of estrone than estradiol. Therefore, transdermal administration of the drug produces therapeutic plasma levels of estradiol with lower levels of estrone and estrone conjugates.

Peak concentration of estradiol = 144 pg mL^-1

Half-life of estradiol = 1 hr

Release rate of estradiol= 0 .1 mg per day

For 36 cm² patch amount of estradiol A = 3.1 mg

Over 84 hr plasma clearance of estradiol = 61 Lh^-1

Volume of distribution is simply proportionality constant between the amount of drug in the body and the concentration of drug measured in a body fluid. It is not a real number that is related to a physical space or volume.

The larger the volume of distribution more likely is that the drug is found in the tissues of the body. The smaller the volume of distribution more likely is that the drug is confined to the circulatory system.

Volume of distribution of estradiol_apparent = Amount in milligram / Concentration in milligrams per litre

                                                = A / C_total

= 3.1 / .000144 in litre

= 21527.77 litre

Volume of distribution V_d is simply proportionality constant between the amount of drug in the body and the concentration of drug measured in a body fluid. It is not a real number that is related to a physical space or volume.

The larger the volume of distribution more likely is that the drug is found in the tissues of the body. The smaller the volume of distribution more likely is that the drug is confined to the circulatory system.