Determination of Dermal Pharmacokinetics by Microdialysis Sampling in Rats

Abstract

The evaluation of absorption and availability at the site of action of a drug candidate is an important element of drug discovery and development, as clinical response is a function of the bioavailability of the active agent and its continued presence at the site of action. Evaluation of dermal pharmacokinetics facilitates the selection of new compounds or chemical structures for advancement as possible clinical candidates. An advantage of microdialysis is that it allows the measurement of compound concentrations at the site of action without disturbing the tissue milieu, making it possible to determine the relationship between this important variable and plasma concentrations of the agent. Described in this unit are laboratory protocols for performing dermal microdialysis experiments in rat for the purpose of defining the pharmacokinetics parameters of test agents. © 2019 by John Wiley & Sons, Inc.

Transdermal delivery of triptolide–phospholipid complex to treat rheumatoid arthritis

“…After the probe was implanted, the implant point and end point were fixed with a medical tape to prevent the probe from moving and the drugs from entering the damaged skin. To avoid the effect of tissue fluid, a flow rate of 1 μL·min −1 was used for blank perfusion (30% ethanol was diluted with normal saline) after probe implantation, and the tissue was balanced for 45 min to recover to normal level (Voelkner et al, 2019 ).…”

Automotive Remanufacturing in a Changing Market : Challenges and Opportunities in a market with a growing share of electric cars

“…All vehicles, whether ICEs, PHEV, HEV or BEVs or others, need a transmission (or gearbox) to convert the power, control it and transmit it to the wheels (Ngo, 2012;Voelkner and Robkhob, 2010).…”

“…If not done in advance by the customer, the oil is drained by opening the drain plugs. The transmission is disassembled completely (Voelkner and Robkhob, 2010). "Missing a worn spline or leaving a small fragment inside a transmission will cause premature failure" (TRC, 2014).…”

In Vitro Permeation Test (IVPT) for Pharmacokinetic Assessment of Topical Dermatological Formulations

“…Dermal bioavailability cannot be reliably estimated from IVPT samples, as factors such as drug clearance from tissue into systemic circulation (Ibrahim, Nitsche, & Kasting, 2012; Kapoor, Milewski, Mitra, & Kasting, 2016) and skin metabolism (Manevski et al., 2015; Oesch, Fabian, Oesch‐Bartlomowicz, Werner, & Landsiedel, 2007; Svensson, 2009) may not be easily determined or mathematically modeled. Use of dermal open‐flow microperfusion (dOFM), with the measurement of drug levels in the dermal interstitial fluid, has been reported as a suitable option for assessment of dermal bioavailability (Bodenlenz, Dragatin, et al., 2016; Bodenlenz, Tiffner, et al., 2017); dermal microdialysis has also been used for such a purpose (Erdo, Hashimoto, Karvaly, Nakamichi, & Kato, 2016; Holmgaard et al., 2012; see Current Protocols article; Voelkner, Voelkner, & Derendorf, 2019).…”