ABCMdb

PMID: 15229462

Sparreboom A, Gelderblom H, Marsh S, Ahluwalia R, Obach R, Principe P, Twelves C, Verweij J, McLeod HL
Diflomotecan pharmacokinetics in relation to ABCG2 421C>A genotype.
Clin Pharmacol Ther. 2004 Jul;76(1):38-44., [PubMed]

Sentences

No. Mutations Sentence Comment

56 ABCG2 p.Gln141Lys ABCC1 p.Ala893Ser ABCC2 p.Val417Ile Frequencies for studied variant genes and genotype-phenotype relationships Polymorphism and nomenclature Effect Allele frequencies Ratio (q/p) for intravenous AUC Ratio (q/p) for oral AUC p q Value† P value Value† P value ABCG2 421CϾA Q141K 0.88 0.12 2.98 .015 1.15 .74 ABCC2-24CϾT 5'-UTR 0.89 0.11 0.868 .82 0.890 .78 ABCC2 1249GϾA V417I 0.86 0.14 1.06 .92 2.10 .063 ABCC2 156231AϾG Intron 3 1.00 0.00 NA NA NA NA ABCB1 1236CϾT‡ (ABCB1*8§) G411G 0.40 0.60 0.877 .82 0.585 .31 ABCB1 2677GϾA/T࿣ (ABCB1*7§) A893S/T 0.63 0.34/0.03 0.784 .61 1.27 .55 ABCB1 3435CϾT‡ (ABCB1*6§) I1145I 0.45 0.55 0.978 .97 0.955 .93 CYP3A4 -392AϾG (CYP3A4*1B) Promotor 0.91 0.09 0.731 .63 0.834 .75 CYP3A4 15713TϾC‡ (CYP3A4*2) S222P 1.00 0.00 NA NA NA NA CYP3A4 23172TϾC (CYP3A4*3) M445T 1.00 0.00 NA NA NA NA CYP3A5 22893GϾA‡ (CYP3A5*3) Splice Variant 0.86 0.14 0.808 .77 0.813 .76 CYP3A5 30597GϾA (CYP3A5*6) Splice Variant 1.00 0.00 NA NA NA NA AUC, Area under plasma concentration-time curve normalized to dose (ie, observed AUC/dose in milligrams); NA, not available. Login to comment 78 ABCG2 p.Gln141Lys Plasma concentration-time profiles of diflomotecan as a function of ABCG2 421CϾA (Q141K) genotype (in which open symbols are homozygous wild-type patients [n ϭ 15] and solid symbols are heterozygous variant patients [n ϭ 5] receiving a 20-minute intravenous infusion of diflomotecan at a dose of 0.1-0.27 mg). Login to comment 87 ABCG2 p.Gln141Lys The studied variant in ABCG2 is a single nucleotide polymorphism causing a nonsynonymous change in the protein sequence, in which a 421C to A transition at exon 5 leads to a lysine to glutamine amino acid substitution at codon 141 (Q141K). Login to comment 91 ABCG2 p.Gln141Lys Area under curve (AUC) of diflomotecan as a function of ABCG2 421CϾA (Q141K) genotype. Login to comment