Abstract
A theoretical pharmacokinetic interaction mediated through L-amino acid transporter 1 and 2 exists between gabapentin (GP) and pregabalin (PG) with melphalan. Peripheral neuropathy is a common toxicity of various multiple myeloma regimens commonly utilized prior to autologous hematopoietic cell transplant (auto-HCT) with high-dose melphalan (HD-Mel). Therefore, it is likely concurrent administration of either GP or PG will occur in patients receiving HD-Mel conditioning for auto-HCT, which could potentially increase cellular uptake and worsen the mucosal injury. A retrospective chart review of adult patients from January 2012 to July 2016 who received HD-Mel (140-200mg/m2) at West Virginia University Medicine was performed to assess toxicity and outcomes in these patients. A total of 80 patients were included in the study, with 30 patients receiving GP or PG and 50 control patients. There were no significant differences in grade 2 or higher mucositis, admissions for nausea/vomiting/diarrhea, intravenous opioid requirements, oral topical therapies, antidiarrheal medication use, rescue anti-emetics, days of nausea or vomiting, pain scores, neutrophil or platelet engraftment, treatment-related mortality, progression-free survival, or overall survival. Our data suggest that it is safe to continue GP/PG therapy throughout HD-Mel therapy, with no negative transplant outcomes. Prospective studies or evaluations of larger databases are necessary to better characterize the clinical effect of concomitant therapy.
Highlights
L-type amino acid transporter 1 (LAT1) and 2 (LAT2) are responsible for the transportation of large neutral amino acids across the intracellular membrane. These transporters appear to have specific drugcarrying functionality with certain medications, which are structurally similar to amino acids, such as gabapentin (GP), pregabalin (PG), melphalan, levodopa, methyldopa, and baclofen.1, LAT1 is primarily found in the brain, placenta, certain tumors, and it may play a role in transport of molecules into growing cells
The purpose of this study was to determine if patients receiving concomitant GP or PG had different toxicities and outcomes with high-dose melphalan (HD-Mel) compared to patients who were not receiving any additional medication known to interact with LAT1/LAT2
We observed a numerical decrease in mucositis, nausea, and vomiting in the GP/PG group
Summary
L-type amino acid transporter 1 (LAT1) and 2 (LAT2) are responsible for the transportation of large neutral amino acids across the intracellular membrane. These transporters appear to have specific drugcarrying functionality with certain medications, which are structurally similar to amino acids, such as gabapentin (GP), pregabalin (PG), melphalan, levodopa, methyldopa, and baclofen., LAT1 is primarily found in the brain, placenta, certain tumors, and it may play a role in transport of molecules into growing cells. In cell-line pharmacokinetic studies, GP significantly inhibited the uptake of amino acids by LAT1 and LAT2. GP transport into cells has previously been demonstrated to be inhibited by the amino acid L-phenylalanine.
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