RESUMO
WHAT IS KNOWN AND OBJECTIVE: Lenvatinib inhibits CYP2C8. (S)-Warfarin is metabolized to (S)-7-hydroxywarfarin by CYP2C9 and (S)-4'-hydroxywarfarin by CYP2C8. Here, we report drug interactions between warfarin and lenvatinib in a patient with CYP2C9*1/*3. CASE SUMMARY: The patient was administered warfarin. His international normalized ratio (INR) was 1.92 before lenvatinib administration. On day 8 after beginning 12 mg/day lenvatinib, plasma trough concentrations of lenvatinib and (S)-warfarin were 33.3 ng/mL and 0.67 µg/mL, respectively. On day 10, his INR increased to 3.48. WHAT IS NEW AND CONCLUSION: Lenvatinib-dependent (S)-warfarin inhibition could involve CYP2C9 and CYP2C8. After initiating warfarin plus lenvatinib, INR assays are necessary.
Assuntos
Citocromo P-450 CYP2C9/genética , Interações Medicamentosas/genética , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Vitamina K Epóxido Redutases/genética , Varfarina/uso terapêutico , Idoso , Citocromo P-450 CYP2C8/genética , Genótipo , Humanos , MasculinoRESUMO
1. The purpose of the present study was to investigate the effect of tacrolimus concentration in blood 12 h after administration (C12h) on acute renal dysfunction in patients with lupus nephritis (LN) taking tacrolimus once daily. 2. Five of the 35 LN patients experienced tacrolimus-induced acute renal dysfunction. 3. The average annual C12h of tacrolimus was higher for patients with events of elevated serum creatinine level than for patients not experiencing these events [6.4 (5.6-8.8) versus 2.8 (2.2-4.6) ng/mL, respectively, p=0.001]. 4. The average annual tacrolimus C12h was higher for patients with CYP3A5*3/*3 (PM) than for patients with the CYP3A5*1 allele (EM) [4.6 (3.2-6.6) versus 2.5 (2.0-3.1) ng/mL, respectively, p=0.002]. 5. The area under the receiver operating characteristic was 0.887, which gave the best sensitivity (80.0%) and specificity (86.7%) at a tacrolimus C12h (average annual C12h or C12h at events) threshold of 5.2 ng/mL. 6. C12h measurements, CYP3A5 genotyping and dose adjustments of tacrolimus should be performed to prevent acute renal dysfunction in LN patients taking tacrolimus once daily.
Assuntos
Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Imunossupressores/efeitos adversos , Nefropatias/induzido quimicamente , Nefrite Lúpica/complicações , Tacrolimo/efeitos adversos , Adolescente , Adulto , Idoso , Área Sob a Curva , Creatinina/sangue , Feminino , Genótipo , Humanos , Imunossupressores/farmacocinética , Estimativa de Kaplan-Meier , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Tacrolimo/farmacocinética , Adulto JovemRESUMO
Actinobacteria produce about two-thirds of all naturally derived antibiotics currently in clinical use. Kitasatospora aureofaciens Tü117 is a species of Actinobacteria and produces α-lipomycin. We report the complete genome sequence of K. aureofaciens, composed of a single linear chromosome of 8,717,539 Mbp with a G + C content of 72.0%.