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• W2024255497 abstract "Abstract 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 (0–100 min) the fraction absorbed (fabs) and effective permeability (Peff) of phenoxymethylpenicillin were 0.3% and 0.06 × 10−4cms−1, 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 10−4cms−1 (0–100 min), respectively, also remaining unchanged by addition of sodium caprate (100–200 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 14.0–62.8 and 56.4–231 (min μ mol L−1) 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." @default.
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• W2024255497 title "The influence of caprate on rectal absorption of phenoxymethylpenicillin: experience from an in-vivo perfusion in humans" @default.
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• W2024255497 doi "https://doi.org/10.1211/0022357021778772" @default.
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