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- Title
PII-59.
- Authors
Yue, C. Seng; Lavigne, J.; Marier, J.; Ducharme, M. P.; Pope, L. E.; Berg, J. E.; Brandt, T. A.; Di Marco, M.
- Abstract
Background: AVP-923 is a combination product of 30 mg dextromethorphan (DM) and 30 mg quinidine (Q) for the treatment of pseudobulbar affect in patients with various neurological disorders.Aim: To evaluate the population pharmacokinetics (PK) of AVP-923 in 170 subjects (53 healthy and 117 patients).Methods: Plasma samples were collected following oral administration of AVP-923 and concentrations of DM, dextrorphan (DX), and Q were assayed. Urine samples were collected for the determination of DM and DX. Compartmental analyses were performed using ADAPT-II®. Data for all analytes/matrices were modeled simultaneously and the impact of various covariates was investigated (age, gender, body weight, and phenotype).Results: The PK of Q was best described by a 1-compartment (CPT) model, while the PK of DM and DX were described by 2-CPT models. The model included a CYP2D6 inhibitory Emax effect driven by Q levels preventing biotransformation of DM to DX and reducing the renal clearances of DM and DX. Age had no effect on the PK of DM. For DX, there was an apparent increase in the central volume of distribution with increasing age. This was likely a reflection of a decrease in the terminal elimination rate constant since total clearance of both DM and DX was unaffected by age. Underlying diseases did not seem to affect the PK of DM or DX.Conclusions: The effect of Q on DM and DX was adequately characterized using an inhibitory Emax function.Clinical Pharmacology & Therapeutics (2005) 79, P51–P51; doi: 10.1016/j.clpt.2005.12.184
- Subjects
PHARMACOKINETICS; CHEMICAL kinetics; EXPERIMENTAL pharmacology; CLINICAL trial registries; CLINICAL drug trials
- Publication
Clinical Pharmacology & Therapeutics, 2006, Vol 79, Issue 2, pP51
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.12.184