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Measurement of oxybutynin and its n-desethyl metabolite in plasma, and its application to pharmacokinetic studies in Young, elderly and frail elderly volunteers

Xenobiotica, ISSN: 0049-8254, Vol: 22, Issue: 7, Page: 859-869
1992
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Article Description

1. A quantitative h.p.l.c. plasma assay for oxybutynin (OB) and its active metabolite, N-desethyl oxybutynin (DEOB) is described. The method is linear with coefficients of variation ranging between 4 and 11.8% for OB and 4.6-9.1% for DEOB over the typical concentration range measured. Minimum detectable levels were 0.5 and 5 ng/ml for OB and DEOB respectively from a 2 ml sample. 2. Pharmacokinetic parameters were obtained after a single oral dose of OB and after administration two or three times daily to frail elderly and elderly volunteer groups respectively. Single dose results were also compared with data from young healthy volunteers. 3. There was a wide range in peak blood levels and high levels of parent drug were matched by high DEOB metabolite levels. Plasma levels on repeated administration were as would be predicted from the single dose kinetics. 4. Area under the plasma time course curve for DEOB metabolite was ≤ 5 than that of the parent drug. 5. A trend of increasing peak plasma levels and bioavailability was observed with increasing age and frailty, with the differences more apparent between the active elderly and frail elderly groups than between the active elderly and young volunteers. 6. Results indicate that for frail elderly patients a lower initial starting dose of 2.5 mg OB given two or three times a day may provide adequate therapeutic blood levels of the drug. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Bibliographic Details

K. M. Hughes; J. C. T. Lang; R. Lazare; D. Gordon; S. L. Stanton; J. Malone-Lee; M. Geraint

Informa UK Limited

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Environmental Science

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