Pharmacokinetic equivalence of 5(ethyl(/sup 2/H)5)- and unlabelled phenobarbitone
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.
- Research Organization:
- Laboratoire D'Etudes Analytiques Et Cinetiques Du Medicament, Lyon (France)
- OSTI ID:
- 6080469
- Journal Information:
- J. Clin. Pharmacol.; (United States), Journal Name: J. Clin. Pharmacol.; (United States) Vol. 29:2; ISSN JCPCB
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AZINES
BARBITURATES
BIOCHEMICAL REACTION KINETICS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHROMATOGRAPHY
DEUTERIUM
DRUGS
GAS CHROMATOGRAPHY
HETEROCYCLIC COMPOUNDS
HYDROGEN ISOTOPES
HYDROXYLATION
HYPNOTICS AND SEDATIVES
ISOTOPE APPLICATIONS
ISOTOPE EFFECTS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MAN
MASS SPECTROSCOPY
NUCLEI
ODD-ODD NUCLEI
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHENOBARBITAL
PRIMATES
PROTEINS
PYRIMIDINES
REACTION KINETICS
REAGENTS
SEPARATION PROCESSES
SPECTROSCOPY
STABLE ISOTOPES
TIME DEPENDENCE
TRACER TECHNIQUES
VERTEBRATES