Buccal absorption of ketobemidone and various ester prodrugs in the rat

L.B. Hansen; A. Jorgensen; S.N. Rasmussen; Lona Louring Christrup; H. Bundgaard

doi:10.1016/0378-5173(92)90322-S

Buccal absorption of ketobemidone and various ester prodrugs in the rat

L.B. Hansen, A. Jorgensen, S.N. Rasmussen, Lona Louring Christrup, H. Bundgaard

6 Citations (Scopus)

Abstract

The buccal absorption of ketobemidone, a strong narcotic analgesic, and various carboxylate and carbonate ester prodrugs was studied in rats. The compounds were administered in the form of aqueous solutions of pH 7.4. The absolute bioavailability of ketobemidone following buccal dosing was 26% whereas the bioavailability of ketobemidone following buccal administration of the prodrugs ranged from 37 to 98%. The highest bioavailability was obtained with the ethyl carbonate ester. An apparent parabolic correlation between bioavailability and lipophilicity of the compounds was seen. All esters were rapidly hydrolyzed to ketobemidone after both buccal and intravenous administration. The acute toxicity of the esters after i.v. administration to mice and rats was similar to that of the parent drug. It is concluded that esterification of the phenolic hydroxyl group in ketobemidone to give a more lipophilic prodrug may be a useful approach to improve the buccal delivery of this analgesic.

Original language	English
Journal	International Journal of Pharmaceutics
Volume	88
Issue number	1-3
Pages (from-to)	243-250
Number of pages	8
ISSN	0378-5173
DOIs	https://doi.org/10.1016/0378-5173(92)90322-S
Publication status	Published - 1 Jan 1992

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title = "Buccal absorption of ketobemidone and various ester prodrugs in the rat",

abstract = "The buccal absorption of ketobemidone, a strong narcotic analgesic, and various carboxylate and carbonate ester prodrugs was studied in rats. The compounds were administered in the form of aqueous solutions of pH 7.4. The absolute bioavailability of ketobemidone following buccal dosing was 26% whereas the bioavailability of ketobemidone following buccal administration of the prodrugs ranged from 37 to 98%. The highest bioavailability was obtained with the ethyl carbonate ester. An apparent parabolic correlation between bioavailability and lipophilicity of the compounds was seen. All esters were rapidly hydrolyzed to ketobemidone after both buccal and intravenous administration. The acute toxicity of the esters after i.v. administration to mice and rats was similar to that of the parent drug. It is concluded that esterification of the phenolic hydroxyl group in ketobemidone to give a more lipophilic prodrug may be a useful approach to improve the buccal delivery of this analgesic.",

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T1 - Buccal absorption of ketobemidone and various ester prodrugs in the rat

AU - Hansen, L.B.

AU - Jorgensen, A.

AU - Rasmussen, S.N.

AU - Christrup, Lona Louring

AU - Bundgaard, H.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - The buccal absorption of ketobemidone, a strong narcotic analgesic, and various carboxylate and carbonate ester prodrugs was studied in rats. The compounds were administered in the form of aqueous solutions of pH 7.4. The absolute bioavailability of ketobemidone following buccal dosing was 26% whereas the bioavailability of ketobemidone following buccal administration of the prodrugs ranged from 37 to 98%. The highest bioavailability was obtained with the ethyl carbonate ester. An apparent parabolic correlation between bioavailability and lipophilicity of the compounds was seen. All esters were rapidly hydrolyzed to ketobemidone after both buccal and intravenous administration. The acute toxicity of the esters after i.v. administration to mice and rats was similar to that of the parent drug. It is concluded that esterification of the phenolic hydroxyl group in ketobemidone to give a more lipophilic prodrug may be a useful approach to improve the buccal delivery of this analgesic.

AB - The buccal absorption of ketobemidone, a strong narcotic analgesic, and various carboxylate and carbonate ester prodrugs was studied in rats. The compounds were administered in the form of aqueous solutions of pH 7.4. The absolute bioavailability of ketobemidone following buccal dosing was 26% whereas the bioavailability of ketobemidone following buccal administration of the prodrugs ranged from 37 to 98%. The highest bioavailability was obtained with the ethyl carbonate ester. An apparent parabolic correlation between bioavailability and lipophilicity of the compounds was seen. All esters were rapidly hydrolyzed to ketobemidone after both buccal and intravenous administration. The acute toxicity of the esters after i.v. administration to mice and rats was similar to that of the parent drug. It is concluded that esterification of the phenolic hydroxyl group in ketobemidone to give a more lipophilic prodrug may be a useful approach to improve the buccal delivery of this analgesic.

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SP - 243

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JO - International Journal of Pharmaceutics

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ER -

Buccal absorption of ketobemidone and various ester prodrugs in the rat

Abstract

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