Relevance of animal models for percutaneous absorption

Wester, Ronald C.; Noonan, Patrick K.

doi:10.1016/0378-5173(80)90054-x

Cited by 98 publications

(31 citation statements)

References 26 publications

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“…From using both in vivo or in vitro studies, human skin has been found to be more impermeable than the skin of other species such as the cat, dog, rat, mouse, or guinea pig Maibach 1977, 1993;Wester and Noonan 1980). Pig or guinea pig skin is favored for use in studies involving diffusion cells (Bronaugh et al 1986;Harrison et al 1984;Reifenrath and Kamppainen 1991) over other animal skin types, whereas skin from the forearm or back is favored in live monkey studies and in studies performed on human volunteers (Feldmann and Maibach 1974).…”

Section: Skin Permeabilitymentioning

confidence: 99%

Parameters for Pyrethroid Insecticide QSAR and PBPK/PD Models for Human Risk Assessment

Knaak

Dary²,

Zhang

et al. 2012

Reviews of Environmental Contamination and Toxicology

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In this review we have examined the status of parameters required by pyrethroid QSAR-PBPK/PD models for assessing health risks. In lieu of the chemical,biological, biochemical, and toxicological information developed on the pyrethroids since 1968, the finding of suitable parameters for QSAR and PBPK/PD model development was a monumental task. The most useful information obtained came from rat toxicokinetic studies (i.e., absorption, distribution, and excretion), metabolism studies with 14C-cyclopropane- and alcohol-labeled pyrethroids, the use of known chiral isomers in the metabolism studies and their relation to commercial products. In this review we identify the individual chiralisomers that have been used in published studies and the chiral HPLC columns available for separating them. Chiral HPLC columns are necessary for isomer identification and for developing kinetic values (Vm,, and Kin) for pyrethroid hydroxylation. Early investigators synthesized analytical standards for key pyrethroid metabolites, and these were used to confirm the identity of urinary etabolites, by using TLC. These analytical standards no longer exist, and muste resynthesized if further studies on the kinetics of the metabolism of pyrethroids are to be undertaken.In an attempt to circumvent the availability of analytical standards, several CYP450 studies were carried out using the substrate depletion method. This approach does not provide information on the products formed downstream, and may be of limited use in developing human environmental exposure PBPK/PD models that require extensive urinary metabolite data. Hydrolytic standards (i.e., alcohols and acids) were available to investigators who studied the carboxylesterase-catalyzed hydrolysis of several pyrethroid insecticides. The data generated in these studies are suitable for use in developing human exposure PBPK/PD models.Tissue:blood partition coefficients were developed for the parent pyrethroids and their metabolites, by using a published mechanistic model introduced by Poulin and Thiele (2002a; b) and log DpH 7.4 values. The estimated coefficients, especially those of adipose tissue, were too high and had to be corrected by using a procedure in which the proportion of parent or metabolite residues that are unbound to plasma albumin is considered, as described in the GastroPlus model (Simulations Plus, Inc.,Lancaster, CA). The literature suggested that Km values be adjusted by multiplying Km by the substrate (decimal amount) that is unbound to microsomal or CYPprotein. Mirfazaelian et al. (2006) used flow- and diffusion-limited compartments in their deltamethrin model. The addition of permeability areas (PA) having diffusion limits, such as the fat and slowly perfused compartments, enabled the investigators to bring model predictions in line with in vivo data.There appears to be large differences in the manner and rate of absorption of the pyrethroids from the gastrointestinal tract, implying that GI advanced compartmental transit models (ACAT) need to be included in PBPK mo...

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Section: Skin Permeabilitymentioning

confidence: 99%

Parameters for Pyrethroid Insecticide QSAR and PBPK/PD Models for Human Risk Assessment

Knaak

Dary²,

Zhang

et al. 2012

Reviews of Environmental Contamination and Toxicology

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“…For example, the clear `false positive' of this study is that the rodent skin dataset produces a more accurate model than pig skin. While this would suggest that rodent skin is more representative of human skin than pig skin, there is a vast body of literature, from [5] onwards, that presents experimental evidence that this is not the case. The work of Potts and Guy [3,16] raises an important issue in the accuracy of small datasets.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, GP predictions from the rodent model are much better than the human naϊve model. This means that the rodent model could be more useful than often thought for predicting human skin permeability [5] . Note that QSAR's ION results were from the human training set.…”

Section: Methodsmentioning

confidence: 99%

“…Various models have been offered by many researchers. Bartek, et al [4] and Wester and Noonan [5] investigated several potential models, including rabbit, miniature swine and rat, and concluded that rabbit skin, and then rat skin, were the most permeable membranes, and that flux denoted as J , that is the rate of permeate transfer from one side to the other, through pig skin most resembled that of the permeation across human skin. Many other workers have also indicated the suitability of porcine (pig) skin, especially from weanling or stillborn animals, as a model for percutaneous absorption [6][7][8][9][10] .…”

Section: Problem Domainmentioning

confidence: 99%

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The application of Gaussian processes in the predictions of permeability across mammalian and polydimethylsiloxane membranes

Sun

Adams²,

Davey³

et al. 2012

AIR

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The problem of predicting the rate of percutaneous absorption of a drug is an important issue, particular with the increasing use of the skin as a means of moderating and controlling drug delivery. One key feature of this problem domain is that human skin permeability to penetrants (often characterised by K p , the permeability coefficient) has been shown to be inherently non-linear when mathematically related to the key physicochemical parameters of penetrants. The aims of the current study were to apply and validate Gaussian process regression methods to datasets for membranes other than human skin, and to explore how the nature of the dataset may influence its analysis. Permeability data for absorption across rodent and pig skin, and polydimethylsiloxane Silastic ® membranes was collected from the literature. Two QSPR methods were applied to compare to the Gaussian process models. The results demonstrated that Gaussian process models with different covariance functions outperform the QSPR model for human, pig and rodent datasets, but in general are not good for Silastic ® membranes. These results suggest that the physicochemical parameters employed in this study might not be appropriate for developing models that represent this membrane. In addition, the results show the size of the datasets, in both absolute and comparative senses, appears to influence model quality.

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“…Problems with obtaining ethical approval for in vivo skin studies, as well as time constraints and expense, have motivated researchers to find an alternative technique for measuring drug permeation through skin. 34 Hence, in vitro drug permeation through skin was introduced as an alternative way to measure drug permeation. Unless the compound is highly lipophilic, the stratum corneum is the limiting step for transdermal drug absorption.…”

Section: Drug Transport Through Rat Skinmentioning

confidence: 99%

Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream

Abdulkarim

Abdullah²,

Chitneni³

et al. 2010

IJN

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Introduction: During recent years, there has been growing interest in use of topical vehicle systems to assist in drug permeation through the skin. Drugs of interest are usually those that are problematic when given orally, such as piroxicam, a highly effective anti-inflammatory, antipyretic, and analgesic, but with the adverse effect of causing gastrointestinal ulcers. The present study investigated the in vitro and in vivo pharmacodynamic activity of a newly synthesized palm oil esters (POEs)-based nanocream containing piroxicam for topical delivery. Methods: A ratio of 25:37:38 of POEs: external phase: surfactants (Tween 80:Span 20, in a ratio 80:20), respectively was selected as the basic composition for the production of a nanocream with ideal properties. Various nanocreams were prepared using phosphate-buffered saline as the external phase at three different pH values. The abilities of these formulae to deliver piroxicam were assessed in vitro using a Franz diffusion cell fitted with a cellulose acetate membrane and full thickness rat skin. These formulae were also evaluated in vivo by comparing their antiinflammatory and analgesic activities with those of the currently marketed gel. Results: After eight hours, nearly 100% of drug was transferred through the artificial membrane from the prepared formula F3 (phosphate-buffered saline at pH 7.4 as the external phase) and the marketed gel. The steady-state flux through rat skin of all formulae tested was higher than that of the marketed gel. Pharmacodynamically, nanocream formula F3 exhibited the highest anti-inflammatory and analgesic effects as compared with the other formulae. Conclusion: The nanocream containing the newly synthesized POEs was successful for transdermal delivery of piroxicam.

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Relevance of animal models for percutaneous absorption

Cited by 98 publications

References 26 publications

Parameters for Pyrethroid Insecticide QSAR and PBPK/PD Models for Human Risk Assessment

Parameters for Pyrethroid Insecticide QSAR and PBPK/PD Models for Human Risk Assessment

The application of Gaussian processes in the predictions of permeability across mammalian and polydimethylsiloxane membranes

Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream

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