Mean Absorption Time

Abstract: The theory is outlined of a procedure for characterizing the time-course of drug absorption by determining the mean absorption time. The procedure requires data of the type normally collected in bioavailability studies.

Abstract: The pharmacokinetic and mean time tissue distribution parameters, after a single 50-mg/kg dose of quercetin administered as intravenous bolus, oral solution, and oral suspension, were determined using rat as an animal model. Following intravenous administration, the elimination rate constant and the elimination half-life were found to be 0.0062 min(-1) and 111 min, respectively. Examining the mean time tissue distribution parameters reflected a strong binding affinity of the drug molecules to both plasma and tissue proteins. In addition, the low permeability rate of drug molecules in the peripheral system was demonstrated. Following the oral administration of the drug, the extent of absorption was greater from solution than from suspension. Moreover, the solution showed a shorter Tmax and a higher Cmax than suspension. The absolute bioavailability for the solution was 0.275 and that for suspension was 0.162. The mean residence time (MRT) and the mean absorption time (MAT) were higher for suspension, reflecting the need for dissolving the drug in order to be absorbed. The mean (in-vivo) dissolution time (MDT(in-vivo)) was 34.5 min. Thus, an oral quercetin formulation that can readily form a drug solution in the gastrointestinal tract may enhance the absorption of the drug.

Abstract: Administration of antibiotics by the inhalational route has become part of standard protocols for treatment of and prophylaxis for Pseudomonal pneumonias in patients with cystic fibrosis For tobramycin, however, limited data are available on the aerosol absorption patterns, and no absolute bioavailability data for tobramycin exist The purpose of this study was to measure the absolute bioavailability and systemic absorption characteristics of tobramycin when administered in high doses by a nebulizer Multiple serum concentrations of tobramycin were measured after administration of an intravenous dose (mean, 29 mg/kg every 6 hours) and after an inhalational dose (56 mg/kg over 1 hour) Inhalational doses were superimposed over the "tail" of a steady-state intravenous dose to improve the sensitivity of the assay procedure (Abbott-TDX) Absolute bioavailability (F) was determined from AUC ratios normalized for dose Model-independent pharmacokinetic parameters (volume of distribution [Vss] and total clearance [CLt]) were determined for each subject Absorption characteristics (absorption rate constant [Ka] and mean absorption time [MAT]) were assessed after calculation of the cumulative fraction of drug absorbed, amount of bioavailable drug, and percent remaining to be absorbed per unit time using the Loo-Riegelman method Three men and three women completed the study, and all received concurrent doses of ceftazidime Mean absolute bioavailability (+/- standard deviation) was 913% (+/- 382), and the rate of absorption into the systemic circulation was consistent with a zero-order model profile for all subjects Mean absorption time values reflected a wide degree of subject variability and ranged from approximately 15 to 150 minutes(ABSTRACT TRUNCATED AT 250 WORDS)