European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Feb 2016
Randomized Controlled TrialPanobinostat PK/PD profile in combination with bortezomib and dexamethasone in patients with relapsed and relapsed/refractory multiple myeloma.
Panobinostat, a potent pan-deacetylase inhibitor, improved progression-free survival (PFS) in patients with relapsed and refractory multiple myeloma when combined with bortezomib and dexamethasone in a phase 3 trial, PANORAMA-1. This study aims to explore exposure-response relationship for panobinostat in this combination in a phase 1 trial, B2207 and contrast with data from historical single-agent studies. ⋯ Apparent panobinostat exposure-AE and exposure-ORR relationships were observed when combined with bortezomib and dexamethasone in the treatment of patients with relapsed and refractory multiple myeloma. The addition of dexamethasone facilitated best response even though plasma exposure of panobinostat was reduced. Combination with a strong enzyme inducer should be avoided in future trials to prevent further reduction of panobinostat exposure.
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Eur. J. Clin. Pharmacol. · Feb 2016
Clinical TrialGenotype and co-medication dependent CYP2D6 metabolic activity: effects on serum concentrations of aripiprazole, haloperidol, risperidone, paliperidone and zuclopenthixol.
Therapeutic drug monitoring (TDM) of antipsychotics can aid in therapy optimization, explaining adverse effects or non-response. One reason for therapeutic failure or adverse effects is caused by genetic variations in the cytochrome P450 drug-metabolizing genes. The aim of this study was to evaluate the impact of CYP2D6 polymorphisms on steady-state serum concentrations of antipsychotics metabolized by CYP2D6, taking into account the co-medication with CYP2D6 inhibitors. ⋯ Even with a small number of patients per antipsychotic, the importance of CYP2D6 genotyping was still clearly stated. This study illustrates the high potential of combining TDM and CYP2D6 genotyping in clinical practice.