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Holve D.L.,Eye Care for Animals | Mundwiler K.E.,Biological Test Center | Pritt S.L.,Absorption Systems
Comparative Medicine | Year: 2011

Laboratory rabbits are commonly used for ocular drug and device studies. The purpose of this study was to determine the incidence of spontaneous ocular lesions in laboratory rabbits with respect to sex, breed, and supplier. We retrospectively evaluated ophthalmic examination records of rabbits screened between April 2008 and April 2010. These 1840 records represented 572 black Dutch belted (DB), 1022 New Zealand white (NZW), and 246 NZW x New Zealand red F1 crosses (WRF1). Rabbits were between 6 and 16 wk of age and had been received from 5 suppliers. Ocular structures evaluated were the cornea, lens, iris and vitreous with respect to sex, breed and supplier. A total of 177 rabbits (9.6%) and 233 eyes (6.3%) were effected. Of total rabbits, 15.3% males and 7.3% females were affected. The most common structure affected was the cornea in 5.7% of rabbits, (DB 11.7%, NZW 3.0%, and NZR 3.3%). The lens at 3.6% was second most common (DB 2.1%, NZW 4.6%, and NZR 3.3%). Both iris (0.2%) and vitreous (0.3%) were not significantly affected. Significant sex-breeder-supplier combinations were: cornea DB supplier D, supplier D females, supplier D males, DB males and NZR females; and lens: NZW females; and at least one affected ocular structure: NZW supplier D, supplier D females, DB males, NZW females, and NZR females. Breed, sex, and supplier were significant variables of ocular lesions in laboratory rabbits. Investigators should consider each of these variables when choosing rabbits for ocular studies. Copyright 2011 by the American Association for Laboratory Animal Science.

Shingaki T.,ADME Research Inc | Hidalgo I.J.,Absorption Systems | Furubayashi T.,Shujitsu University | Sakane T.,Kyoto Pharmaceutical University | And 3 more authors.
Drug Metabolism and Pharmacokinetics | Year: 2011

The objective of this study was to evaluate in rats the potential utility of the nasal route to enhance central nervous system (CNS) delivery of drugs recognized by P-glycoprotein (P-gp). Well-known P-gp substrates verapamil and talinolol were perfused nasally or infused intravenously, and when plasma concentrations following intravenous infusion and nasal perfusion showed similar profiles. The concentration of verapamil in the brain after nasal perfusion was twice that after intravenous infusion. Although talinolol in the brain and the cerebrospinal fluid after i.v. infusion were below the detection limit, it was detected after nasal perfusion. When rats were treated with cyclosporin A, brain concentrations of verapamil after both administration modes were increased significantly, while those of talinolol were not significantly changed. Since the permeability of talinolol is low, talinolol in the brain which was transported directly from the nasal cavity has little chance of transport by P-gp localized in the apical membrane of cerebral microvessel endothelial cells. The potential for drug delivery utilizing the noseCNS route was confirmed for P-gp substrates. The advantage of nasal delivery over i.v. delivery of talinolol to the brain was more significant than that of verapamil, suggesting that nasal administration is more useful strategy for the brain delivery of low-permeability P-gp substrates than the use of P-gp inhibitors. © 2011 by the japanese society for the study of xenobiotics (jssx).

News Article | November 21, 2016

EXTON, Pa., Nov. 21, 2016 /PRNewswire/ -- Absorption Systems, a world leader in novel test systems for drug transporters, announces the renewal of a technology licensing deal with Biogen. After years of contract testing by Absorption Systems using MDR1-MDCK cells, Biogen licensed the...

News Article | February 16, 2017

EXTON, Pa., Feb. 16, 2017 /PRNewswire/ -- Absorption Systems, a global leader in nonclinical testing of drugs, biologics, and medical devices, is pleased to announce that its Chief Operating Officer, Sid Bhoopathy, Ph.D., has been selected as a winner of the 2017 Executive Management...

EXTON, Pa., Nov. 11, 2016 /PRNewswire/ -- Absorption Systems, a global leader in the science of translational medicine, announces the issuance of a U.S. patent for its unique In Vitro Dissolution Absorption System (IDAS2™) technology, which enables the simultaneous evaluation of drug...

Miezeiewski B.,Absorption Systems | McLaughlin A.,Absorption Systems
Methods in Pharmacology and Toxicology | Year: 2014

The hepatic transporters OATP1B1 and OATP1B3 contribute (to varying degrees, depending on the drug) to the uptake of many anionic drugs, including several of the widely used statins. Because statins are prescribed for many patients and the consequences of pharmacokinetic interactions with uptake inhibitors can be severe (even fatal), the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require that all NCEs be evaluated as inhibitors of OATP1B1 and OATP1B3. In addition, if hepatic clearance is expected to be a major pathway of elimination of an NCE, it must also be evaluated as a substrate of both transporters. Cell-based assays with over-expressing cell lines are useful for screening both substrates (based on uptake of the test compound) and inhibitors (based on interference with the uptake of a probe substrate by the test compound). The approach will be illustrated with real data, and subtle but important technical details will be discussed. © 2014 Springer Science+Business Media New York.

Wang Y.,Absorption Systems | Behler N.,Absorption Systems
Methods in Pharmacology and Toxicology | Year: 2014

The human transporters organic anion transporter 1 (OAT1), organic anion transporter 3 (OAT3) and organic cation transporter 2 (OCT2) are membrane proteins involved in the renal clearance of substances from the body. While the original purpose of these clearance pathways was likely the removal of naturally occurring metabolism byproducts, they are also responsible for secretion of many drugs. Various assay systems have been developed to study the interactions of drugs with these transporters as either substrates or inhibitors, since a reduction in drug clearance (due to inhibition of transport of one drug by a co-administered drug) could result in elevated exposure and toxicity. This chapter will provide a brief background on the transporters and how they function, highlight the importance of using in vitro test systems to evaluate the potential for drug-drug interactions (DDIs), and provide a detailed procedure for an assay using transfected human embryonic kidney (HEK293) cells. © 2014 Springer Science+Business Media New York.

Bode C.,Absorption Systems | Li L.-B.,Absorption Systems
Methods in Pharmacology and Toxicology | Year: 2014

The organ distribution and substrate specificity of breast cancer resistance protein (BCRP), the product of the human ABCG2 gene, overlaps considerably with that of P-glycoprotein. Both are up-regulated in some cancers, leading to drug resistance, and can mediate drug-drug interactions when two drugs, one a substrate and the other an inhibitor or substrate of the same transporter, are co-administered. Thus, the U.S. FDA and the EMA now require that all NCEs be evaluated as substrates and inhibitors of BCRP. This chapter will cover in vitro assays for human BCRP, including cell-based (over-expressing and knockdown cells) and subcellular (membrane vesicle) approaches; the advantages of intact cells for discerning the complex interplay among the various uptake and efflux transporters will be discussed. Only recently have cell lines become available in which human BCRP is over-expressed; the advantages and limitations of this model will be illustrated. The uses and limitations of existing pharmacologic reagents, and the importance of pairing a given probe substrate with the appropriate biological model, will be discussed and illustrated as well. © 2014 Springer Science+Business Media New York.

Wang Q.,Absorption Systems | Sauerwald T.M.,Absorption Systems
Methods in Pharmacology and Toxicology | Year: 2014

P-glycoprotein (P-gp), the product of the human ABCB1 gene and often called MDR1, is the best understood membrane protein known to be involved in the active transport of drugs across biological membranes. In addition to mediating or limiting the absorption, distribution, excretion, and toxicity of many drugs, P-gp is the potential locus of a number of pharmacokinetic drug-drug interactions when two drugs, one a substrate and the other a substrate or inhibitor of the transporter, are co-administered. This last point is the reason for the interest of regulatory authorities around the world, several of which (most notably the U.S. FDA and the EMA) now require that all new molecular entities (NMEs) be evaluated as P-gp substrates and inhibitors. This chapter will cover model test systems, including in vitro assays for human P-gp such as cell-based (over-expressing and knockdown cells) and subcellular (membrane vesicle) approaches, as well as in vivo animal models. The chapter will conclude with examples of two cell-based systems, MDR1-MDCK (over-expressing) and Caco-2 (parental and P-gp knockdown cell lines). © 2014 Springer Science+Business Media New York.

PubMed | Absorption Systems
Type: Comparative Study | Journal: Drug delivery | Year: 2015

The objective of the study was the optimization of nanoemulsion formulations to prevent their rapid systemic clearance after intravenous administration. An amphiphilic PEG derivative DSPE-PEG (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(polyethylene glycol) with different chain lengths and concentration was used as a nanoemulsion droplet surface modifier. The danazol loading in all nanoemulsions was kept on the same level of 2mg/mL. In the present investigation, PEGylated and non-PEGylated nanoemulsions were compared in vitro phagocytosis by incubating with lung macrophages and in vivo after intravenous administration in rats. Danazol-containing nanoemulsions (NE) modified with various PEG chain lengths (2000-10000) and concentrations (3-12mg/mL) were prepared and characterized. Nanoemulsion droplets were reproducibly obtained in the size range of 213-340nm. The non-PEGylated NE had the surface charge of -25.4mV. This absolute charge value decreased with increasing chain length and concentration. With increase in chain length and density the macrophage uptake decreased which could be due to decrease in surface charge and hydrophilicity of droplets. The greatest shielding of the NE droplets was reached with DSPE-PEG5000 at the concentration of 6mg/mL where the surface charge changed to -1.27mV. Following intravenous administration a maximum danazol exposure (40168.2hng/mL) was observed with the lowest clearance rate (5.060.95L/h/kg) from 6mg/mL DSPE-PEG5000 nanoemulsion. PEG5000 and PEG10000 altered the pharmacokinetic of danazol by decreasing clearance and volume of distribution which is likely explained by the presence of hydrophilic shields around the droplets that prevent their rapid systemic clearance and tissue partitioning.

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