Utility of Göttingen minipigs for Prediction of Human Pharmacokinetic Profiles After Dermal Drug Application

Abstract

Predictions using in vitro skin permeability data in Göttingen minipig skin can reproduce the human pharmacokinetic profile, although the prediction of in vivo skin absorption underestimates human absorption.

Application of the Tissue Composition–Based Model to Minipig for Predicting the Volume of Distribution at Steady State and Dermis-to-Plasma Partition Coefficients of Drugs Used in the Physiologically Based Pharmacokinetics Model in Dermatology

“…The V ss in male minipigs aged 3 months of the strain Nippon Institute of Biological Science (NIBS) was predicted with the TCM for 19 marketed drugs for which complete data sets were available from the literature. 2,[34][35][36][37][38] Furthermore, 19 proprietary compounds from Nestl e Skin Health R&D were also investigated for which intravenous PK have been investigated in male G€ ottingen minipigs aged 9 months and for which all physicochemical and binding parameters have been determined experimentally during our routine screening in drug discovery. These 2 data sets used for V ss predictions are presented in Table 4.…”

Porcine Prediction of Pharmacokinetic Parameters in People: A Pig in a Poke?

“…As we noted above, "The minipig is the species of choice to investigate dermal absorption in preclinical drug development" (Preube and Skaanild, 2012). The intent of this brief review of dermal absorption is to focus on several publications that have evaluated transdermal drug absorption comparing in vitro and in vivo data in the pig (Yamamoto et al, 2017;Yoshimatsu et al, 2017). We also provide in-house data generated at Guangzhou Dazhou Biomedicines (unpublished data) to illustrate the development of an IVIVC to demonstrate the utility of this approach.…”

“…Transdermal IVIVC in Pigs. Yamamoto et al (2017) studied several drugs (nicotine, rivastigmine diclofenac, and lidocaine) in vivo in four minipigs (5 months; 10.0-14.4 kg; breed not reported) by application of the dermal product to the back of the pig. Cryopreserved excised Göttingen minipig skin (male; 5 months; 9.3 kg) was cut from the back of the minipig and dermatomed to a thickness of 400-600 mm.…”

“…Ultimately, if experimental protocols can be standardized (such as pig breed, dermatome methodology, storage of skin, Franz cell setup, etc.) and generally agreed upon, and the in vitro data are found to have adequate correlation to in vivo results, then human skin studies need not be done, that is, prediction of human PK directly based on in vitro pig permeability, as demonstrated by Yamamoto et al (2017). Yoshimatsu et al (2017) conducted in vitro and in vivo studies on six drugs (ketoprofen, flurbiprofen, diclofenac, buprenorphine, fentanyl, and lidocaine) in mice, rats, minipigs, and humans [diclofenac and lidocaine data from the Yamamoto et al 2017study].…”

“…Yoshimatsu et al (2017) conducted in vitro and in vivo studies on six drugs (ketoprofen, flurbiprofen, diclofenac, buprenorphine, fentanyl, and lidocaine) in mice, rats, minipigs, and humans [diclofenac and lidocaine data from the Yamamoto et al 2017study]. The study protocols were basically the same as in Yamamoto et al (2017). The results indicated considerably lower in vitro and in vivo permeability in pigs compared with the other species, including humans.…”