Lack of a pharmacokinetic drug-drug interaction with venlafaxine extended-release/indinavir and desvenlafaxine extended-release/indinavir

Mercer University College of Pharmacy and Health Sciences, 3001 Mercer University Dr., Atlanta, GA 30341, USA.
European Journal of Clinical Pharmacology (Impact Factor: 2.97). 12/2011; 68(5):715-21. DOI: 10.1007/s00228-011-1180-7
Source: PubMed


To assess the effects of venlafaxine extended-release (XR) capsules and desvenlafaxine extended-release (XR) tablets upon indinavir pharmacokinetic properties when co-administrated to healthy volunteers.
This was an open-label, two-period, fixed-dose study conducted at the clinical research unit located on a university campus. Twenty-four healthy volunteers enrolled in the study (mean age 28.3 ± 8.0 years). Each subject received a single dose of indinavir 800 mg on day 1. Subsequently, subjects were then randomly assigned to either the venlafaxine XR group (N = 12) or the desvenlafaxine XR group (N = 12). Starting on day 2, venlafaxine XR was dosed at 37.5 mg/day for 4 days and increased to 75 mg/day for 6 days. Desvenlafaxine XR was dosed at 50 mg/day for 10 days. On day 12, indivanvir 800 mg was co-administered to both the venlafaxine XR and the desvenlafaxine XR groups. The pharmacokinetics of indinavir were determined both before and at the end of antidepressant dosing. Plasma indinavir, venlafaxine, and desvenlafaxine concentrations were assayed by high-performance liquid chromatography with ultra-violet (UV) detection. Indinavir pharmacokinetic parameters were calculated by noncompartmental analysis using validated computer software.
Venlafaxine XR and desvenlafaxine XR did not produce any significant changes in indinavir disposition. Both antidepressants were well tolerated by the subjects with only minor adverse side effects.
No pharmacokinetic drug-drug interaction was demonstrated between venlafaxine XR and indinavir or between desvenlafaxine XR and indinvair. The lack of interaction could be due to the venlafaxine and desvenlafaxine extended-release formulation.

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Available from: Kathryn M Momary, Apr 13, 2015
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    ABSTRACT: Abstract Venlafaxine (VEN) is an antidepressant agent widely used nowadays as an alternative to selective serotonin reuptake inhibitors (SSRIs), particularly for the treatment of SSRI-resistant depression. As the co-administration of antidepressant drugs with other medications is very common in clinical practice, the potential risk for pharmacokinetic and/or pharmacodynamic drug interactions that may be clinically meaningful increases. Bearing in mind that VEN has exhibited large variability in antidepressant response, besides the individual genetic background, several other factors may contribute to those variable clinical outcomes, such as the occurrence of significant drug-drug interactions. Indeed, the presence of drug interactions is possibly one of the major reasons for interindividual variability, and their anticipation should be considered in conjugation with other specific patients' characteristics to optimize the antidepressant therapy. Hence, a comprehensive overview of the pharmacokinetic- and pharmacodynamic-based drug interactions involving VEN is herein provided, particularly addressing their clinical relevance.
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