Pharmacokinetic equivalence of 5(ethyl(2H)5)- and unlabelled phenobarbitone.
J Clin Pharmacol
; 29(2): 168-73, 1989 Feb.
Article
en En
| MEDLINE
| ID: mdl-2715374
ABSTRACT
The present study shows the absence of in vivo pharmacokinetic isotope effect on phenobarbitone (PB) C5-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 less than or equal to 5%); which the absence of pentadeuteration-induced alteration in PB's HSA binding parameters (binding mode, Ka, N) corroborates (x less than or equal to 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.
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Banco de datos:
MEDLINE
Asunto principal:
Fenobarbital
Límite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Pharmacol
Año:
1989
Tipo del documento:
Article
País de afiliación:
Francia