Population in vitro-in vivo correlation model for pramipexole slow-release oral formulations.
OBJECTIVE
To establish an in vitro-in vivo level A correlation (IVIVC) for pramipexole slow-release formulations.


METHODS
The IVIVC was developed based on data from an immediate-release (IR) and three slow-release (SR) formulations of pramipexole; a fourth SR formulation was used for validation purposes. In vitro dissolution profiles were obtained from all SR formulations. Fifteen volunteers received all pramipexole formulations in a randomized cross-over trial. Data were analyzed using the population modelling approach as implemented in NONMEM VI.


RESULTS
Dissolution profiles of the SR formulations were described by the Weibull model. The pharmacokinetics of the IR formulation were described by a two-compartment disposition model with first-order absorption. Difference between the in vivo and in vitro estimates of the release rate constants (k(d)) from the Weibull function suggests the release process occurs faster in vivo. Pharmacokinetic profiles for SR formulations were described based on the in vitro release model with k(d) increased in 0.058 h(-1) and the population pharmacokinetic model developed from the IR formulation.


CONCLUSIONS
A level A IVIVC was established and evaluated for the pramipexole SR formulations, which can be used in the future as a surrogate to avoid certain bioequivalence studies.
Soto
Elena
E
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, 31080, Spain.
Haertter
Sebastian
S
Koenen-Bergmann
Michael
M
Staab
Alexander
A
Trocóniz
Iñaki F
IF
D000284:Administration, Oral; D000293:Adolescent; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D006801:Humans; D008875:Middle Aged; D008956:Models, Chemical; D000077487:Pramipexole; D012995:Solubility
D052160:Benzothiazoles; D003692:Delayed-Action Preparations; D000077487:Pramipexole