RESUMEN
BACKGROUND: There is little data on mycophenolic acid (MPA) pharmacokinetics and pharmacogenomics and optimal MPA exposure in lupus nephritis (LN) patients during long-term maintenance. METHODS: We measured blood MPA levels at 1, 2, 4, 8, 10 and 12-h post-dose (i.e. C1, C2, C4, C8, C10 and C12) in 88 stable LN patients receiving maintenance prednisolone and mycophenolate mofetil, repeated every 6 months. The relationship between MPA exposure and single nucleotide polymorphisms (SNPs) of adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2; rs2273697, rs3740066, rs717620 and rs17222723), organic anion-transporting polypeptides (OATPs; rs7311358 and rs4149117) and uridine diphosphate glucuronosyltransferase (UGT; rs17863762, rs6714486, rs17868320 and rs72551330) was also investigated. RESULTS: C1, C2 and C12 were 8.3 ± 6.6 , 7.2 ± 5.2 and 2.0 ± 1.4 mg/L and all correlated with the 12-h area under the curve (AUC0-12; r = 0.51, 0.85 and 0.73; P = 0.02, <0.001 and <0.001, respectively). C12 inversely correlated with hemoglobin, immunoglobulins and leukocyte levels (P < 0.05 for all). Five renal flares, 11 episodes of infection and 10 episodes of anemia (hemoglobin <10 g/dL) occurred over 96 weeks, with a corresponding C12 of 1.3 ± 0.5, 4.3 ± 2.6 and 2.9 ± 1.5 mg/L, respectively (versus 2.4 ± 1.2, 1.8 ± 1.2 and 1.7 ± 1.1 mg/L in patients without these complications; P = 0.041, <0.001 and 0.004). SNP rs2273697 A/G in the ABCC2 gene was associated with lower MPA exposure compared with G/G (1075.9 ± 239.9 versus 1891.5 ± 918.9 mgh/L per g/kg; P = 0.003). SNPs of OATP and UGT were unrelated to MPA level. CONCLUSION: MPA C12 correlates with the AUC0-12 and is related to renal flare, infection and anemia. SNP rs2273697 A/G is associated with lower MPA exposure.
Asunto(s)
Inmunosupresores/farmacocinética , Nefritis Lúpica/tratamiento farmacológico , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Ácido Micofenólico/farmacocinética , Transportadores de Anión Orgánico/genética , Farmacogenética , Polimorfismo de Nucleótido Simple , Adulto , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/sangre , Nefritis Lúpica/sangre , Nefritis Lúpica/genética , Nefritis Lúpica/patología , Masculino , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/sangre , Estudios Prospectivos , Distribución TisularRESUMEN
OBJECTIVE: To investigate the oral health condition and saliva flow of southern Chinese patients with Sjögren's syndrome (SS). METHOD: 51 SS patients (26 primary and 25 secondary cases) and 29 controls took part in this cross-sectional study. Stimulated whole and parotid saliva flow rates, pH, and buffer capacity, and xerostomia, oral mucosal lesions, oral hygiene status, dental and periodontal conditions, prosthetic status were assessed and compared between groups. RESULTS: Stimulated whole saliva (SWS) flow was reduced in primary and secondary SS cases (p<0.001), pH and buffer capacity were also reduced in the primary SS group (p<0.05). SS patients had a greater prevalence of xerostomia than controls (p<0.001). Primary SS patients had a higher mean DMFT, more missing teeth, and more prostheses than secondary SS cases and controls (p<0.05). SWS flow correlated negatively with the number of filled teeth in both SS groups (p<0.05) and the number of decayed teeth in the primary SS group (p<0.05). CONCLUSION: Despite good oral hygiene and regular dental check-ups, the oral health of southern Chinese with primary SS was significantly compromised compared with secondary SS cases and controls, most probably due to the combined effect of impaired salivary gland function and poorer saliva buffer capacity.