Pharmacokinetics is the study of absorption, distribution, metabolism, and elimination (ADME) of drugs inside the body. Before alendronate can be absorbed by the intestines, it must be released from its dosage form (eg a tablet) and dissolved in the stomach. Availability of the drug to body tissues depends on the physical and chemical characteristics of the drug and the formulation (e.g. nature of the additional ingredients that make up the pharmaceutical formulation).
The term "bioavailability" refers to the fraction of the dose administered that enters systemic circulation. During drug development, scientists study the dissolution and absorption of the material in the body and try to establish the fraction of the particular dosage form available for biological absorption. Physiologists term the bioavailability factor F. For example, if 100 mg of a drug is administered and only 70 mg reaches systemic circulation, then F is 0.7.
To establish pharmacokinetic parameters, scientists give a patient the medicine and collect blood samples. Cmax is the maximum concentration. The time it occurs is referred to as Tmax.
The rate at which a drug is absorbed determines Tmax.
The "area under the curve " (area under or below the concentration curve versus time) or AUC is considered representative of the total amount of drug absorbed. The bioavailability (F) of a drug can be determined by the ratio between the AUC for a particular dosage form and AUC for intravenous administration of the same dose; ,F = AUC other dosage form / AUC intravenous form.
Experimentally, the information derived from the drug versus time tests allows pharmacokinetic parameters to be obtained - volume of distribution, half-life, and clearance. These parameters are used to determine dosage regimens. The apparent volume of distribution ( Vd ) is a hypothetical volume of fluid (extracellular or intracellular) because the actual volume in which the drug is distributed cannot be determined. It is obtained by the ratio of the concentration of drug administered intravenously (D = administered dose) and the concentration of drug in the blood or plasma ( C P ): Vd = D / C P. The volume of distribution may be expressed as a volume or as a percentage of body weight. Experimental data for most drugs indicate that elimination, absorption and distribution are generally directly proportional to the following a first-order kinetics. The elimination constant ( kel ) corresponds to the fraction of drug eliminated per unit of time and is equivalent to the slope of the graph of the logarithm of drug concentration versus time. It can be determined by following equation: kel = 0.693 / t1 / 2 , where t1 / 2 is the half-life of the drug. The half-life ( t1 / 2 ) is the time it takes for the plasma concentration of the drug to fall to half the initial concentration (50%). Clearance ( CL ) is defined as the volume of plasma from which the drug is completely removed per unit of time (units volume per time).
The total clearance of a drug is equal to the sum of the clearances effected by each organ involved in elimination (e.g. liver, kidney). Knowing the time of and the volume of distribution at clearance can be determined from the following form: LC = 0.693 x Vd / t1 / 2 . Summarizing, calculating the slope of the graph of the concentration versus the time, which gives us the kel elimination constant, it is possible to calculate the half-time life t1 / 2 , clearance CL and volume of distribution Vd.
