{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:45:00Z","timestamp":1789994700353,"version":"4.0.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2002,4,1]],"date-time":"2002-04-01T00:00:00Z","timestamp":1017619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The aim of this in-vivo perfusion study in humans was to investigate the influence of a penetration enhancer, sodium caprate, on the rectal absorption of phenoxymethylpenicillin and antipyrine. Six subjects, 3 male and 3 female, were included in two separate studies using perfusion solution of different pH (T1 and T2, respectively). Each in-vivo rectal perfusion investigation lasted for 200 min and consisted of two periods of 100 min, the first serving as a control, and sodium caprate being added in the second period in both T1 and T2. The concentrations of phenoxymethylpenicillin, antipyrine and sodium caprate in the outlet perfusate were assayed by HPLC, as was the plasma concentrations of phenoxymethylpenicillin. At pH 6.0 (0\u2013100 min) the fraction absorbed (fabs) and effective permeability (Peff) of phenoxymethylpenicillin were 0.3% and 0.06 \u00d7 10\u22124cms\u22121, respectively, and remained unaffected by the addition of sodium caprate. When the same subjects were perfused at pH 7.4, the fabs and Peff of phenoxymethylpenicillin were 2.4% and 0.11 times 10\u22124cms\u22121 (0\u2013100 min), respectively, also remaining unchanged by addition of sodium caprate (100\u2013200 min). It was possible to determine the plasma AUC of phenoxymethylpenicillin after addition of sodium caprate in three subjects at both pHs; this was in the range of 14.0\u201362.8 and 56.4\u2013231 (min \u03bc mol L\u22121) at pH 6.0 and 7.4, respectively. Interestingly, there was a correlation between Peff for sodium caprate and the individual plasma AUC and Cmax of phenoxymethylpenicillin, which indicates that the permeability of the enhancer in the tissue upon which it should act is crucial for achieving an effect. The fabs and the Peff of antipyrine were not affected at either pH when sodium caprate was added to the perfusion solution. In conclusion, the plasma pharmacokinetics of phenoxymethylpenicillin suggested a slightly increased rectal absorption at pH 7.4 in subjects where sodium caprate was transported into the rectal tissue. However, the increased Peff for phenoxymethylpenicillin was too small to detect from the outlet perfusate, which suggests that sodium caprate alone has a limited effect on the permeability in-vivo across the rectal epithelium when it is presented in a solution.<\/jats:p>","DOI":"10.1211\/0022357021778772","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T20:14:04Z","timestamp":1034367244000},"page":"499-508","source":"Crossref","is-referenced-by-count":33,"title":["The influence of caprate on rectal absorption of phenoxymethylpenicillin: experience from an in-vivo perfusion in humans"],"prefix":"10.1093","volume":"54","author":[{"given":"H","family":"Lennern\u00e4s","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Biopharmaceutics division, Uppsala University ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Gjellan","sequence":"additional","affiliation":[{"name":"Pharmaceutical R&D, Astra L\u00e4kemedel AB , 151 85 S\u00f6dert\u00e4lje,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"H\u00e4llgren","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Uppsala University ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Graffner","sequence":"additional","affiliation":[{"name":"Pharmaceutical R&D, Astra L\u00e4kemedel AB , 151 85 S\u00f6dert\u00e4lje,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,4,1]]},"reference":[{"key":"2024103109380908200_cit1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1023\/A:1016212804288","article-title":"Theoretical considerations in the correlation of drug product dissolution and in vivo bioavailability: a biopharmaceuticaldrug classification","volume":"12","author":"Amidon","year":"1995","journal-title":"Pharm. Res."},{"key":"2024103109380908200_cit2","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/jps.2600810908","article-title":"Epithelial transport of drugs in cell culture. VII. Effects of pharmaceutical surfabsctant excipients and bile acids on transepithelial permeability in monolayers of human intestinal epithelial (Caco-2) cells","volume":"81","author":"Anderberg","year":"1992","journal-title":"J. Pharm. Sci."},{"key":"2024103109380908200_cit3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/jac\/43.2.177","article-title":"The suppository form of antibiotic administration: pharmacokinetics and clinical application","volume":"43","author":"Bergogne-B\u00e9r\u00e9zin","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"2024103109380908200_cit4","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1177\/030006058801600507","article-title":"Clinical evaluation of rectally administered ampicillin in acute otitis media","volume":"16","author":"Bergstr\u00f6m","year":"1988","journal-title":"J. Int. Med. Res."},{"key":"2024103109380908200_cit5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/jps.2600730125","article-title":"Lumen perfusion of the human rectum in situ: a method to study mechanisms for rectal drug transport in humans","volume":"73","author":"B\u00f6ttger","year":"1984","journal-title":"J. Pharm. Sci."},{"key":"2024103109380908200_cit6","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/bdd.2510130608","article-title":"Extended least squares curve fitting: a comparison of SIPHAR and MKMODEL","volume":"13","author":"Cockshott","year":"1992","journal-title":"Biopharm. Drug Dispos."},{"key":"2024103109380908200_cit7","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0169-409X(92)90004-A","article-title":"Rate controlled rectal peptide absorption enhancement, In Penetration enhancement for polypeptides through epithelia","volume":"8","author":"de Boer","year":"1992","journal-title":"Adv. Drug Delivery Rev."},{"key":"2024103109380908200_cit8","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1136\/gut.11.5.438","article-title":"Failure of the human rectum to absorb electrolytes and water","volume":"11","author":"Devroede","year":"1970","journal-title":"Gut"},{"key":"2024103109380908200_cit9","first-page":"193","article-title":"Comparative study on ampicillin bioavailability from capsule and suppositories","volume":"54","author":"Farouk","year":"1984","journal-title":"Acta Pharm. Hung."},{"key":"2024103109380908200_cit10","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0939-6411(98)00041-1","article-title":"Biopharmaceutical characterization of oral immediate release drug products. In vitro\/in vivo comparison of ***phenoxymethyl penicillin potassium, glimepiride and levofloxacin","volume":"46","author":"Frick","year":"1998","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"2024103109380908200_cit11","first-page":"2711","volume-title":"Development of new adjuvants for enhanced rectal absorption","author":"Kakeya","year":"1985"},{"key":"2024103109380908200_cit12","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/j.2042-7158.1997.tb06084.x","article-title":"Human jejunal effective permeability and its correlation to preclinical drug absorption models","volume":"49","author":"Lennern\u00e4s","year":"1997","journal-title":"J. Pharm. Pharmacol."},{"key":"2024103109380908200_cit13","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1023\/A:1016216905197","article-title":"Regional rectal perfusion, a new in vivo approach to study rectal drug absorption in man","volume":"12","author":"Lennern\u00e4s","year":"1995","journal-title":"Pharm. Res."},{"key":"2024103109380908200_cit14","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1111\/j.2042-7158.1997.tb06092.x","article-title":"A RTD analysis of the hydrodynamics within the human intestine during a regional single-pass perfusion: in vivo permeability estimation","volume":"49","author":"Lennern\u00e4s","year":"1997","journal-title":"J. Pharm. Pharmacol."},{"key":"2024103109380908200_cit15","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0009-9236(96)90145-9","article-title":"Jejunal permeability and hepatic extraction of fluvastatin in humans","volume":"60","author":"Lindahl","year":"1996","journal-title":"Clin. Pharmacol. Ther."},{"key":"2024103109380908200_cit16","first-page":"958","article-title":"Mechansims of absorption enhancement by medium chain fatty acids in intestinal epithelial Caco-2 cell monolayers","volume":"275","author":"Lindmark","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2024103109380908200_cit17","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1023\/A:1012112219578","article-title":"Mechanism of absorption enhancement in humans after rectal administration of ampicillin in suppositories containing sodium caprate","volume":"14","author":"Lindmark","year":"1997","journal-title":"Pharm. Res."},{"key":"2024103109380908200_cit18","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0006-2952(99)00377-9","article-title":"Effects of sodium deoxycholate and sodium caprate on the transport of epirubucin in human intestinal epithelial Caco-2 cell layers and everted gut sacs of rats","volume":"59","author":"Lo","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"2024103109380908200_cit19","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1093\/jnci\/82.21.1679","article-title":"Expression of the MDR1 gene in human gastric and colorectal carcinomas J","volume":"82","author":"Mizoguchi","year":"1990","journal-title":"Natl Cancer Inst."},{"key":"2024103109380908200_cit20","first-page":"1453","article-title":"A technique for segmental rectal and colonic perfusion in humans","volume":"10","author":"Raab","year":"1992","journal-title":"Am. J. Gastroenterol."},{"key":"2024103109380908200_cit21","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1023\/A:1015840921203","article-title":"Role of paracellular pathway in nonelectrolyte permeation across rat colon epithelium enhanced by sodium caprate and sodium caprylate","volume":"8","author":"Sawada","year":"1991","journal-title":"Pharm. Res."},{"key":"2024103109380908200_cit22","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000238260","article-title":"Rectal bioavailability of bacampicillin hydro-chloride in man as determined by reversed-phase liquid chromatography","volume":"30","author":"Sj\u00f6wall","year":"1984","journal-title":"Chemotherapy"},{"key":"2024103109380908200_cit23","volume-title":"Transport and diffusion across cell membranes","author":"Stein","year":"1986"},{"key":"2024103109380908200_cit24","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1248\/bpb.20.446","article-title":"The enhancing mechanism of capric acid (C10) from a suppository on rectal drug absorption through a paracellular pathway","volume":"20","author":"Takahashi","year":"1997","journal-title":"Biol. Pharmacol. Bull."},{"key":"2024103109380908200_cit25","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1023\/A:1015992819290","article-title":"Enhancement of colonic drug absorption by the transcellular permeation route","volume":"5","author":"Tomita","year":"1988","journal-title":"Pharm. Res."},{"key":"2024103109380908200_cit26","first-page":"76","article-title":"Rectal absorption enhancement of rate-controlled delivered ampicillin sodium by sodium decanoate in conscious rats","volume":"10","author":"van Hoogdaalem","year":"1988","journal-title":"Pharm Weekbl. Sci. Ed."},{"key":"2024103109380908200_cit27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1365-2125.1989.tb05337.x","article-title":"Rate-controlled rectal absorption enhancement of cefoxitin by co-administration of sodium salicylate or sodium octanoate in healthy volunteers","volume":"27","author":"van Hoogdaalem","year":"1989","journal-title":"Br. J. Clin. Pharmacol."},{"key":"2024103109380908200_cit28","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2165\/00003088-199121010-00002","article-title":"Pharmacokinetics of rectal drug administration. General considerations and clinical applications of centrally acting drugs. Part 1","volume":"21","author":"van Hoogdaalem","year":"1991","journal-title":"Clin. Pharmacokinet."},{"key":"2024103109380908200_cit29","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1021\/jm9810102","article-title":"Correlation of human jejunal permeability (in vivo) with experimentally and theoretically derived parameters. A multivariate data analysis approach J","volume":"41","author":"Winiwarter","year":"1999","journal-title":"Med. 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