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Statistical Methods for Assessment of Complex Generic Drugs
Published in Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow, Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
Since acyclovir cream, 5% is a product with modest efficacy, comparative studies with clinical endpoints would be resource-consuming and not feasible to perform. The FDA PSG for acyclovir cream recommends an IVPT-based BE study (US FDA, 2016a). Although a novel technique, dermal open flow microperfusion (dOFM), can provide a direct in vivo measurement of drug concentration at or near the site of action in the skin and thereby characterize the rate and extent of drug exposure (Bodenlenz et al., 2017), this method may not as feasible and economical as IVPT. Furthermore, dOFM devices are still yet to be approved for utilization in human in some country up to date. Currently, IVPT have been used in a number of pre-clinical studies and bioavailability studies.
Collecting antibodies and large molecule biomarkers in mouse interstitial brain fluid: a comparison of microdialysis and cerebral open flow microperfusion
Published in mAbs, 2021
Florie Le Prieult, Erica Barini, Loic Laplanche, Kerstin Schlegel, Mario Mezler
To date, microdialysis is the only in vivo method enabling the continuous measurement of free, unbound analyte concentrations in the ISF. Thoroughly investigated in several tissues (brain, liver, skin, kidney, and muscle) for small chemical molecules up to peptides, mainly in rodents,7–9 and less frequently in humans,10,11 this minimally invasive sampling technique is currently being adapted to collect large biotechnological molecules, including mAbs. Indeed, sampling and quantitatively measuring macromolecules (mAbs are ~150 kDa) in ISF necessitates a sampling unit with large openings. Only two distinct ISF-sampling units currently offer this possibility: microdialysis (MD) probes, consisting of a large molecular weight cutoff (MWCO) membrane of ~1 MDa, and a novel type called cerebral open flow microperfusion (cOFM) probes, consisting of an open exchange structure formed of a macroscopic plastic mesh. Because probes with large openings bring experimental challenges, which can strongly affect the peri-probe environment,12,13 only a few groups in the scientific community have so far investigated the PK of large molecules, including mAbs, in the rodent brain ISF using the large pore MD probe.14,15 Their work started to validate MD for the collection of macromolecules and opened the path to new insights into understanding the brain disposition of mAbs. However, as method validation for MD probes continues with new equipment entering the market and novel challenges identified, the use of cOFM probes offers an opportunity to broaden the possibilities.
Revisiting techniques to evaluate drug permeation through skin
Published in Expert Opinion on Drug Delivery, 2021
Vamshi Krishna Rapalli, Arisha Mahmood, Tejashree Waghule, Srividya Gorantla, Sunil Kumar Dubey, Amit Alexander, Gautam Singhvi
This method assumes that the recovery efficiency of the analyte of interest and the marker are quantitatively similar. During the experiment, any fluctuations in the probe’s recovery can be overcome by constant retrodialysis of the marker [39]. Open-flow microperfusion is a slight variant of the microdialysis technique as it utilizes probes having macroscopic openings instead of the porous membrane [10]. The study affords real-time monitoring. The invasiveness is the main drawback of the microdialysis technique. In potent drugs, it required sensitive analytical techniques to estimate the drug content in few cases.
Dermato-pharmacokinetic: assessment tools for topically applied dosage forms
Published in Expert Opinion on Drug Delivery, 2021
Vamshi Krishna Rapalli, Gautam Singhvi
A microdialysis and open-flow microperfusion techniques are employed to assess the bioequivalence of the topical drug product. The drug concentration is determined in the dermis and hypodermis by implanting a semipermeable membrane probe guided by a needle. The probe is perfused with the sterile buffer, which mimics the blood vessels, equilibrates by interstitial fluids, and the drug molecules diffuse from tissues to the buffer. Isotonic saline/Ringer’s lactate solution is perfused at the rate of 1–5 µL [11,12]. Figure 1 depicts the microdialysis and tape striping technique.