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Evaluating the Pharmacokinetics and Systemic Effects of a Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl)amino] Caprylate in Rats.
J Pharm Sci. 2020 Aug; 109(8):2629-2636.JP

Abstract

Oral administration is the preferred route for drug delivery and its success is highly dependent on a compound's ADME properties, of which, permeability plays a major role. Therefore, permeability enhancers are an attractive area of research in the pharmaceutical industry. Recent data suggest that sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) is an effective permeability enhancer, yet the pharmacokinetic (PK) and systemic effects of SNAC are poorly understood, specifically its oral bioavailability and systemic effects on distribution, which could influence the safety of certain drugs. To answer these questions, both in vitro and in vivo studies were conducted. Of 3 permeability enhancers (SNAC, 4-CNAB, and 5-CNAC), SNAC was found to have the greatest effect on the absorption of cyanocobalamin in rats. It was also found that SNAC is orally bioavailable (almost 40%) when dosed to rats. Based on these findings, tool compounds were co-dosed in rats to further evaluate the systemic effects of SNAC. Oral co-dosing of SNAC with an intravenous infusion of 2 poorly brain penetrant compounds, quinidine, and gabapentin, did not increase brain ISF: plasma ratio or total brain:plasma ratio for either of these compounds, implying that SNAC is effective only in the intestine at pharmacologically relevant concentrations.

Authors+Show Affiliations

Small Molecule Pharmaceutical Sciences, Genentech Inc, 1 DNA Way, South San Francisco, California 94080.Drug Metabolism and Pharmacokinetics, Genentech Inc, 1 DNA Way, South San Francisco, California 94080.Small Molecule Pharmaceutical Sciences, Genentech Inc, 1 DNA Way, South San Francisco, California 94080.Small Molecule Pharmaceutical Sciences, Genentech Inc, 1 DNA Way, South San Francisco, California 94080.Drug Metabolism and Pharmacokinetics, Genentech Inc, 1 DNA Way, South San Francisco, California 94080.IVS Group, Genentech Inc, South San Francisco, California 94080.Drug Metabolism and Pharmacokinetics, Genentech Inc, 1 DNA Way, South San Francisco, California 94080.Drug Metabolism and Pharmacokinetics, Genentech Inc, 1 DNA Way, South San Francisco, California 94080.Drug Metabolism and Pharmacokinetics, Genentech Inc, 1 DNA Way, South San Francisco, California 94080. Electronic address: durkm@gene.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32360544

Citation

Chiang, Po-Chang, et al. "Evaluating the Pharmacokinetics and Systemic Effects of a Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl)amino] Caprylate in Rats." Journal of Pharmaceutical Sciences, vol. 109, no. 8, 2020, pp. 2629-2636.
Chiang PC, Deshmukh G, Liu J, et al. Evaluating the Pharmacokinetics and Systemic Effects of a Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl)amino] Caprylate in Rats. J Pharm Sci. 2020;109(8):2629-2636.
Chiang, P. C., Deshmukh, G., Liu, J., Nagapudi, K., Chen, J. Z., Valle, N., Li, R., Plise, E. G., & Durk, M. R. (2020). Evaluating the Pharmacokinetics and Systemic Effects of a Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl)amino] Caprylate in Rats. Journal of Pharmaceutical Sciences, 109(8), 2629-2636. https://doi.org/10.1016/j.xphs.2020.04.016
Chiang PC, et al. Evaluating the Pharmacokinetics and Systemic Effects of a Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl)amino] Caprylate in Rats. J Pharm Sci. 2020;109(8):2629-2636. PubMed PMID: 32360544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluating the Pharmacokinetics and Systemic Effects of a Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl)amino] Caprylate in Rats. AU - Chiang,Po-Chang, AU - Deshmukh,Gauri, AU - Liu,Jia, AU - Nagapudi,Karthik, AU - Chen,Jacob Z, AU - Valle,Nicole, AU - Li,Ruina, AU - Plise,Emile G, AU - Durk,Matthew R, Y1 - 2020/04/28/ PY - 2020/01/31/received PY - 2020/04/06/revised PY - 2020/04/22/accepted PY - 2020/5/4/pubmed PY - 2020/5/4/medline PY - 2020/5/4/entrez KW - Blood-brain barrier KW - Distribution KW - Permeability KW - Permeation enhancer(s) KW - Pharmacokinetics SP - 2629 EP - 2636 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 109 IS - 8 N2 - Oral administration is the preferred route for drug delivery and its success is highly dependent on a compound's ADME properties, of which, permeability plays a major role. Therefore, permeability enhancers are an attractive area of research in the pharmaceutical industry. Recent data suggest that sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) is an effective permeability enhancer, yet the pharmacokinetic (PK) and systemic effects of SNAC are poorly understood, specifically its oral bioavailability and systemic effects on distribution, which could influence the safety of certain drugs. To answer these questions, both in vitro and in vivo studies were conducted. Of 3 permeability enhancers (SNAC, 4-CNAB, and 5-CNAC), SNAC was found to have the greatest effect on the absorption of cyanocobalamin in rats. It was also found that SNAC is orally bioavailable (almost 40%) when dosed to rats. Based on these findings, tool compounds were co-dosed in rats to further evaluate the systemic effects of SNAC. Oral co-dosing of SNAC with an intravenous infusion of 2 poorly brain penetrant compounds, quinidine, and gabapentin, did not increase brain ISF: plasma ratio or total brain:plasma ratio for either of these compounds, implying that SNAC is effective only in the intestine at pharmacologically relevant concentrations. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/32360544/Evaluating_the_Pharmacokinetics_and_Systemic_Effects_of_a_Permeability_Enhancer_Sodium_N-[8-(2-hydroxybenzoyl)amino]_Caprylate_in_Rats L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(20)30239-2 DB - PRIME DP - Unbound Medicine ER -
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