Influence of the UGT2B7 -161C>T polymorphism on the population pharmacokinetics of lamotrigine in Thai patients

Abstract

Both genetic and non-genetic factors were found to influence lamotrigine pharmacokinetics. These factors should be considered when determining lamotrigine dosing. The model presented here could be useful for lamotrigine dose adjustment in clinical practice.

Rash and multiorgan dysfunction following lamotrigine: could genetic be involved?

“…In Caucasians, there are two polymorphisms that lead to amino acid changes, UGT1A4 70C[A (rs#: 6755571) and the UGT1A4 142T[G (rs#: 2011425), with allelic frequencies of 4.9-8.8 and 8.3-11 %, respectively [17,19,20]. They are in linkage disequilibrium and have been associated with reduced in vitro glucuronidation activities against different substrates, including LTG [15,17,19,[21][22][23]. Our patient was homozygous for UGT1A4-70C, and this cannot account for higher LTG levels, since patients carrying this wild-type genotype would exhibit a higher clearance.…”

“…Moreover, it been suggested that, beside other factors (e.g., age, concurrent disease, body size, co-medications, pregnancy status, ethnicity), also UGT1A4, UGT2B7 and ABCB1 variants may also influence the pharmacokinetics of LTG and, consequently, explain its inter-individual variability [15][16][17].…”

“…It contributes to the glucuronidation of LTG and other antiepileptic drugs [15]. Several polymorphisms have been detected within the UGT2B7 gene, and they have been associated to changes in glucuronidation activities.…”

“…Several polymorphisms have been detected within the UGT2B7 gene, and they have been associated to changes in glucuronidation activities. The two most common are UGT2B7 161C[T (rs#: 7668258) and 372A[G (rs#: 7662029), with allelic frequencies in Caucasians of 49-56 and 3-13 %, respectively [15,16,22,[24][25][26].…”

“…Among UGT1s, UGT1A4 is of major importance in the conjugation and subsequent elimination of various therapeutic drugs, including LTG [15,17]. The UGT1A4 gene is highly polymorphic, with 109 SNPs described so far [17,18].…”