Title
Pharmacokinetics of oestriol after repeated oral administration to dogs
Author
Hoeijmakers, M.
Janszen, B.
Coert, A.
Horspool, L.
TNO Voeding
Publication year
2003
Abstract
The aim of the present study was to investigate the pharmacokinetics of oestriol in plasma in the dog after repeated oral administration of oestriol tablets, a preparation intended for the treatment of urinary incontinence in the bitch. The study was performed in six healthy, entire, adult female beagle dogs. The bitches were treated once daily with two tablets, containing 1 mg oestriol per tablet, for seven consecutive days (days 1-7). Blood samples were taken from the jugular vein before treatment, frequently on days 1, 3 and 7 of the treatment period and daily just before (Ctrough) and 1 h after dosing (Ct=1h). During the washout period samples were taken at a 24 h interval up to four days post-treatment. Oestriol concentrations were determined in plasma by radioimmunoassay. Pharmacokinetic parameters, AUC, Cmax and tmax, were determined from the plasma concentration-time curves using non-compartmental methods. The between animal variation in Cmax and the AUC was high. Individual values of the Cmax varied from 206 pg/ml (day 1) to 1128 pg/ml (day 7) and the AUC0-24 h from 789 pg.h/ml (day 1) to 5718 pg.h/ml (day 7). tmax occurred within 1 h. The mean Ctrough value was slightly above the pre-treatment level (38 ± 2 pg/ml vs. 18 ± 5 pg/ml). Within 48 h after the last treatment the concentrations had returned to the pre-treatment values. Cmax, and Ctrough did not increase during the treatment period, indicating that no accumulation occurred. A shoulder in the concentration-time curve around 8-12 h after treatment strongly suggested the existence of enterohepatic recirculation (EHR). The average relative contribution of the EHR to the AUC0-24 h was estimated to be 22%, 38% and 44% on days 1, 3 and 7, respectively. These mean values were calculated from five animals per time point, because one dog failed to show EHR on days 1 and 3 and was therefore excluded from the calculations. © 2003 Elsevier Science Ltd. All rights reserved.
Subject
Drugs Chemistry
Physiological Sciences
estriol
incurin
animal experiment
area under the curve
article
blood sampling
calculation
controlled study
dog
dose response
drug accumulation
drug blood level
enterohepatic circulation
female
individualization
nonhuman
radioimmunoassay
statistical analysis
tablet formulation
urine incontinence
Administration, Oral
Animals
Dogs
Estriol
Female
Urinary Incontinence
Animalia
Canidae
Canis familiaris
To reference this document use:
http://resolver.tudelft.nl/uuid:a95f4594-6cef-47d1-87b4-230367206490
DOI
https://doi.org/10.1016/s0034-5288(03)00032-8
TNO identifier
237195
ISSN
0034-5288
Source
Research in Veterinary Science, 75 (1), 55-59
Document type
article