Absolute bioavailability

Absolute bioavailability. Absolute bioavailability is used as a measure of the efficiency of the absorption of the drug. It is defined in terms of the total dose of the drug the body would receive if the drug were placed directly in the general circulation by an I.V. bolus injection, that is ... 

Pharmacokinetic and bioavailability (absolute and relative) experiments are usually designed and conducted to evaluate dose proportionality over the dose range used, or expected to be used, in toxicology studies and possible species-to-species differences in pharmacokinetic profiles. With the incorporation of one or two I.V. dose levels into the study protocol, the drug candidate s absolute... 

Bioavailability (absolute) was based on AUCtopicai/AUCrv, with correction for dose. GFI = glycerol-formal/isopropanol mixture. 

L d Agay-Abensour, A Fjellestad-Paulsen, P Hoglund, Y Ngo, O Paulsen, JC Rambaud. Absolute bioavailability of an aqueous solution of l-deamino-8-D-argi-nine vasopressin from different regions of the gastrointestinal tract in man. Eur J Clin Pharmacol 44 473-476, 1993. 

Whenever a drug is administered by an extra-vascular route, there is a danger that part of the dose may not reach the blood (i.e., absorption may not be complete). When the intravenous route is used, the drug is placed directly in the blood therefore an IV injection is, by definition, 100% absorbed. The absolute bioavailability of an extravascular dosage form is defined relative to an IV injection. If IV data are not available, the relative bioavailability may be defined relative to a standard dosage form. For example, the bioavailability of a tablet may be defined relative to an oral solution of the drug. 

If dosage form 2 [Eq. (42)] is an intravenous dosage form, the absolute bioavailability of the extravascular dosage form (dosage form 1) is given by ... 

Absolute bioavailability AUCextravascuiar (extravascular dosage form) AUCiv... 

Assuming that the AUC for a 100 mg IV dose given to the same group of volunteers was 86.7h.pg/mL, the absolute bioavailability of the extravascular dosage form is... 

Example. When potassium penicillin G was administered IV to a group of volunteers, 80% of the 500 mg dose was recovered unchanged in urine. When the same drug was administered orally to the same volunteers, 280 mg was recovered unchanged in urine. What is the absolute bioavailability of potassium penicillin G following oral administration From Eq. (47),... 

In these cases it is not necessary to determine the absolute bioavailability or the absorption rate constant for the product under study. It is only necessary to prove that the plasma concentration versus time curve is not significantly different from the reference product s curve. This is done by comparing the means and standard deviations of the plasma concentrations for the two products at each sampling time using an appropriate statistical test. 

Dopamine, a vasodilator, has been widely used for treatment of acute circulatory failure. However, since dopamine is rapidly metabolized when administered orally, its use has been limited to intravenous infusion. Murata et al., studied the bioavailability and the pharmacokinetics of orally administered dopamine (DA). The oral administration of DA to dogs resulted in an absolute bioavailability of approximately 3%. To minimize the extensive first-pass metabolism of DA, a dopamine prodrug, V-(/V-acetyl-l-mcLhionyl)-o,o-bis(cLhoxycarbonyl)dopamine (TA-870), was synthesized [28] (Fig. 6). Since DA is a substrate for both mono-... 

WD Mason, N Winer, G Kochak, I Cohen, R Bell. Kinetics and absolute bioavailability of atenolol. Clin Pharmacol Ther 25 408-415, 1979. 

M Pfeffer, RC Gaver, J Ximenez. Human intravenous pharmacokinetics and absolute oral bioavailability of cefatrizine. Antimicrob Agents Chemother 24 915-920, 1983. 

Freeman GB, Johnson JD, Liao SC, et al. 1994. Absolute bioavailability of lead acetate and mining waste lead in rats. Toxicology 91 151-163. 

Pharmacokinetic Definition of Intestinal Absorption (fa), Presystemic Metabolism (Ec and Eh) and Absolute Bioavailability (F) of Drugs Administered Orally to Humans... 

The most useful pharmacokinetic variable for describing the quantitative aspects of all processes influencing the absorption (fa) and first-pass metabolism and excretion (Eg and Eh) in the gut and liver is the absolute bioavailability (F) [40]. This pharmacokinetic parameter is used to illustrate the fraction of the dose that reaches the systemic circulation, and relate it to pharmacological and safety effects for oral pharmaceutical products in various clinical situations. The bioavailability is dependent on three major factors the fraction dose absorbed (fa) and the first-pass extraction of the drug in the gut wall (EG) and/or the liver (EH) (Eq. (1)) [2-4, 15, 35] ... 

Fig. 19.2. Comparison of absolute oral bioavailability between humans and monkeys [8].

It is important to remember that absolute oral bioavailability is a function of both absorption and first-pass metabolism. Therefore, a linear approach to predicting absolute oral bioavailability based on a single parameter, such as rate or extent of absorption (fraction of dose absorbed or estimated dose absorbed) or the rate of metabolism (microsomal or hepatic intrinsic clearance), may result in an inaccu-... 

Sietsema, W. K., The absolute oral bioavailability of selected drugs, Int. J. Clin. Pharmacol. Ther. Toxicol. 1989,... 

According to the FDA BCS guideline, measurements of the permeability and fraction dose absorbed of a drug can be made by mass balance, absolute bioavailability or intestinal perfusion methods. The intestinal permeability of a drug can be determined by ... 

Soul-Lawton, J., Seaber, E., On, N., Wootton, R., Roian, P., Posner, J., Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of acyclovir, following oral administration to humans, Antimicrob. Agents Chemother. 1995, 39, 2759— 2764. 

---