Search results for "Subfamily B"
showing 10 items of 125 documents
Unusual high dose of tacrolimus in liver transplant patient, a case report.
2012
Case We describe the case of a liver transplant patient who had great difficulty in reaching the desired trough blood levels despite the use of high dose tacrolimus. The patient was homozygous for the CYP3A5*3 allele. However, the respective donor carried the wild-type CYP3A5*1/*1 genotype. Regarding ABCB1 SNPs at exon 21 and 26, the patient showed the 2677GT and 3435CC genotypes. For the corresponding donor we observed the 2677GG and 3435CC wild-type genotypes. One, two and three weeks after transplantation the patient received daily 0.219, 0.287 and 0.273 mg/kg of tacrolimus, respectively. However, the corresponding tacrolimus trough blood levels were of 4.6, 5.6 and 6.1 ng/mL. The tacrol…
Association of SNPs with the efficacy and safety of immunosuppressant therapy after heart transplantation.
2015
Aim: Studying the possible influence of SNPs on efficacy and safety of calcineurin inhibitors upon heart transplantation. Materials & methods: In 60 heart transplant patients treated with tacrolimus or cyclosporine, we studied a panel of 36 SNPs correlated with a series of clinical parameters during the first post-transplantation year. Results: The presence of serious infections was correlated to ABCB1 rs1128503 (p = 0.012), CC genotype reduced the probability of infections being also associated with lower blood cyclosporine concentrations. Lower renal function levels were found in patients with rs9282564 AG (p = 0.003), related to higher blood cyclosporine blood levels. A tendency tow…
Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans – Implications for the evaluation of …
2013
Quercetin has been shown to inhibit intestinal P-glycoprotein-mediated drug efflux. A crossover clinical study was performed in 10 healthy volunteers to assess the effect of single-dose and repeated quercetin intake on the pharmacokinetics of talinolol, a substrate of intestinal P-glycoprotein. Unexpectedly, mean area under the plasma concentration-time curve (AUC0-48h) and maximal plasma concentration (cmax) were slightly decreased following concomitant and short-term quercetin administration (3186.0 versus 2468.3 and 2527.7 ng h/ml, p>0.05; 309.7 versus 212.0 and 280.6 ng/ml, p>0.05). Individual analysis revealed that talinolol AUC0-48h was lowered by 23.9% up to 60.6% in 5 subjects and c…
Effects of controlled-release on the pharmacokinetics and absorption characteristics of a compound undergoing intestinal efflux in humans
2006
Abstract Objective The number of active pharmaceutical ingredients (API) undergoing inhibitable and saturable intestinal efflux is considerable. As a consequence, absorption and bioavailability may depend on the intestinal concentration profile of the drug and may vary as a function of dose and release rate of the drug from the dosage form. The impact of controlled versus immediate-release on the absorption of P-glycoprotein substrates is currently unknown. Thus, the main focus of the present study was a comparison of the pharmacokinetics of the P-gp model substrate talinolol following administration of immediate-release (IR) and controlled-release (CR) tablets to healthy human volunteers w…
Correlation between GP-170 expression, prognosis, and chemoresistance of superficial bladder carcinoma.
2003
To study GP-170 in superficial bladder cancer at initial diagnosis and at recurrence and to evaluate if intravesical chemoprophylaxis modifies the expression of GP-170 in tumor recurrences. GP-170 was retrospectively assessed in 160 patients affected by primary superficial transitional cell carcinoma of the bladder and followed for up to 10 years. Eighty-four patients (52.5%) recurred after transurethral resection (TUR). Adjuvant intravesical chemotherapy after TUR was adopted in 52 patients. The correlations between GP-170 and G-grade, T-category, risk of recurrence and of progression, and adoption of adjuvant intravesical chemotherapy were investigated. The correlations between variations…
Influence of ABCB1 polymorphisms upon the effectiveness of standard treatment for acute myeloid leukemia: A systematic review and meta-analysis of ob…
2015
The ABCB1 gene encodes for P-glycoprotein (P-gp), an efflux pump for a variety of xenobiotics. The role of ABCB1 polymorphisms in acute myeloid leukemia (AML) outcomes of standard chemotherapy (cytarabine plus anthracyclines) remains controversial. A systematic search was made of studies evaluating the association between ABCB1 polymorphisms 1236C>T, 2677G>T/A and 3435C>T and effectiveness variables. We found seven cohort studies (1241 patients) showing a significantly higher overall survival (OS) among carriers of the variant allele of 1236C>T at year 4 (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.07-2.01), 2677G>T/A at years 4-5 (OR: 1.37, 95% CI: 1.01-1.86) and 3435C>T at year…
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective ana…
2014
Abstract Background Mitoxantrone is used on an off-label basis in primary progressive MS (PPMS). ABC -transporter-genotypes are associated with therapeutic response in relapsing/secondary progressive MS (RP/SPMS). Objective To evaluate potential pharmacogenetic response markers for mitoxantrone in PPMS. Methods 41 mitoxantrone-treated PPMS-patients, 155 mitoxantrone-treated RP/SPMS-patients and 43 PPMS-controls were retrospectively assessed for clinical therapy-response and in correlation with four single-nucleotide-polymorphisms in ABCB1 - and ABCG2 -genes. Results 53.7% PPMS-patients were mitoxantrone-responders, in comparison to 78.1% of RP/SPMS-patients (p = 0.039). There was no associa…
Defects in the Human Leukocyte Antigen Class I Antigen Processing Machinery in Head and Neck Squamous Cell Carcinoma: Association with Clinical Outco…
2005
AbstractPurpose: Human leukocyte antigen (HLA) class I antigen defects, which are frequently present in head and neck squamous cell carcinoma (HNSCC) cells may provide the tumor with an escape mechanism from immune surveillance. Scanty information is available about mechanisms underlying HLA class I antigen defects in both lesions and cell lines from HNSCC. In this study, we investigate the role of antigen processing machinery (APM) component abnormalities in the generation of deficient HLA class I surface expression of HNSCC cells.Experimental Design: Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the expression of the IFN-γ inducible proteasome subunits and of…
Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients
2011
Tacrolimus is a substrate of cytochrome P4503A (CYP3A) enzymes as well as of the drug transporter ABCB1. We have investigated the possible influence of CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) and other factors (e.g. albumin, hematocrit and steroids) on tacrolimus blood levels achieved in a population of Caucasian liver (n=51) and kidney (n=50) transplant recipients. At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were recorded and the weight-adjusted tacrolimus dosage (mg/kg/day) was calculated. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*1 and *3 …
Association Between ABCB1 Genetic Variants and Persistent Chemotherapy-Induced Alopecia in Women With Breast Cancer
2020
Importance Persistent chemotherapy-induced alopecia (pCIA) has been recently described in patients with breast cancer and in its most severe form occurs in up to 10% of these patients. Genetic risk factors associated with pCIA have not been adequately explored. Objective To identify genetic variants associated with pCIA. Design, Setting, and Participants In this genetic association study, 215 women with breast cancer treated with docetaxel-based chemotherapy with a follow-up of 1.5 to 10 years after the end of the treatment were recruited retrospectively through 3 hospital oncology units across Spain between 2005 and 2018. Severe pCIA was defined as lack of scalp hair recovery (Common Termi…