On pharmacokinetics in target tissues

Abstract

Based on a two-compartment organ model the total exposure in a target tissue, the mean tissue residence time and the peak time of the tissue concentration are evaluated in terms of tissue to blood partition coefficient and permeability coefficient (membrane permeability) of the drug, as well as the organ volume and blood flow. The total exposure is dependent upon the partition coefficient whereas the mean residence time is also affected by the permeability coefficient of the target organ. The peak time of tissue concentration following bolus intravenous injection appears to be mainly determined by the mean organ transit time and the time course of blood concentration. A tissue specific therapeutic ratio is defined using the concept of total exposure and the advantages of a local route of drug administration are discussed in this respect.

Dermal and Underlying Tissue Pharmacokinetics of Lidocaine after topical application

“…where AUCT,, is the area under the tissue concentration-time profile, AUC, is the area under the plasma concentration-time profile, and RMT, is the tissue-plasma partition coefficient. 16 The MINIM computer programI7 was used to numerically integrate eqs 5,7, and 9 (using the concentration-time data in underlying tissues) or 10 (using the underlying tissue concentration minus contralateral tissue concentration data) and simultaneously fit the lidocaine data obtained as the solution for cell, dermis, subcutaneous tissue, and fascia using weighted (l/Ci) least squares with Hartley modification of the Gauss-Newton algorithm. A sixth order polynomial input function representation of the observed solute concentrations in the plasmatime profiles was used.…”

Pharmacokinetics of amikacin in serum and in tissue contiguous with pressure sores in humans with spinal cord injury

“…This approach can provide an acceptable fit of experimental results. In general, however, such models tend to oversimplify in vivo phenomena (21,29,46,47) and fail to account for nonlinear pharmacokinetic behavior. Our data suggest that the nonlinear processes that influence the disposition of highly protein-bound drugs should also be anticipated for poorly protein-bound antibiotics, such as amikacin (26).…”

Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution

“…In vivo data were characterised using model-independent pharmacokinetic analysis [18]. The calculated pharmacokinetic parameters were: total area under the curve (AUC 0 ∞ ), plasma clearance (Cl), apparent distribution volume (Vd), mean residence time (MRT), and plasma or tissue half-life (t 1/2 ).…”