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Pharmacokinetic Equivalence of 5(ethyl( 2 H) 5 )‐ and Unlabelled Phenobarbitone
Author(s) -
Benchekroun Y.,
Ribon B.,
Falconnet J. B.,
Cherrah Y.,
Brazier J. L.
Publication year - 1989
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1989.tb03308.x
Subject(s) - pharmacokinetics , bioequivalence , chemistry , bioavailability , urine , in vivo , chromatography , pharmacology , isotope , biochemistry , medicine , physics , microbiology and biotechnology , quantum mechanics , biology
The present study shows the absence of in vivo pharmacokinetic isotope effect on phenobarbitone (PB) C 5 ‐ethyl deuteration (PBd5) following oral administration to man of equimolar PB/PBd5 mixtures (0.40 mmol each). Plasma PB and PBd5 (17 days) and urine PB, PBd5 and parahydroxy‐metabolites (PBOH, PBHOd5) levels were determined by GC‐MS. Isotope effect research includes comparison of pharmacokinetic parameters, study of time‐dependence of isotope ratios (IRs) in plasma and urine (linearity test), comparison of IRs between samples and administered mixtures (Mann Whitney's test) and comparison of PBOH/PBOHd5 ratios before and after urine enzymatic hydrolysis (Student's two tailed t‐test). No significant isotope effect was observed on pharmacokinetic parameters, PB hydroxylation or PBOH conjugation (x ≤ 5%); which the absence of pentadeuteration‐induced alteration in PB's HSA binding parameters (binding mode, Ka, N) corroborates (x ≤ 5%). These results establish bioequivalence of PB and PBd5; the latter can be used with benefit in stable‐isotope clinical pharmacology (steady state pharmacokinetics, drug interactions …) investigations as well as bioavailability studies of PB preparations.