Biomedical subjects

Gwyn Lord

Publications and source records attributed to Gwyn Lord.

4 recordsLinked to original sources

PubMed2004

Medication use, tamoxifen (TAM), and TAM metabolite concentrations in women with breast cancer.

Tamoxifen (TAM) is commonly used as an adjuvant treatment for breast cancer. Although patients taking TAM are often taking medications for comorbidities, data regarding the interaction of TAM with other medications are limited. Thus, this study was carried out to determine whether medications co-prescribed with TAM significantly influence the plasma concentrations of TAM and its metabolites (N-desmethyltamoxifen; N-DMT and 4-hydroxytamoxifen; 4-OHT) in 98 women diagnosed with breast cancer. Participants taking diuretics had significantly higher plasma concentrations of TAM and N-DMT than participants not taking a diuretic. Arthritis/pain medication intake was negatively associated with plasma TAM concentrations. Chemotherapeutic agents, allergy drugs, anti-depressants, and diabetes medications did not significantly alter plasma TAM or metabolite concentrations. This suggests that diuretic or an arthritis/pain medication may affect TAM metabolism.

Anti-Allergic Agents↗

PubMed2004

Association of tamoxifen (TAM) and TAM metabolite concentrations with self-reported side effects of TAM in women with breast cancer.

The positive effects of tamoxifen (TAM) on breast cancer recurrence and survival as well as on overall mortality have led to its use as the predominant adjuvant therapy among women with breast cancer. However, the association of TAM intake with undesirable side effects has been reported in numerous studies. This analysis was carried out to assess whether the concentrations of TAM or TAM metabolites, N -desmethyltamoxifen ( N -DMT) and 4-hydroxytamoxifen (4-OHT), were associated with self-reported side effects of TAM. Participants were 99 breast cancer patients who had been taking TAM for at least 30 days. Each participant completed a questionnaire that was used to ascertain whether she experienced certain specific symptoms while taking TAM. In addition, each woman provided a blood sample that was used to measure plasma concentrations of TAM, N -DMT, and 4-OHT by high performance liquid chromatography. Results of the analysis showed that women who experienced at least one TAM-related side effect had significantly higher levels of TAM than women not experiencing any TAM-related side effects. Furthermore, women who reported experiencing visual problems had significantly higher levels of both TAM and N -DMT compared to those women who reported experiencing no visual problems. The levels of 4-OHT were negatively associated with the occurrence of vaginal discharge. The results of this study suggest that the self-reported occurrence of certain symptoms during TAM treatment is related to TAM metabolism. Future studies should assess subgroups of women with specific TAM and TAM metabolite profiles to determine whether alternate, equally effective therapies would decrease their risk of experiencing certain undesirable side effects.

Antineoplastic Agents, Hormonal↗

PubMed2003

Aging may be associated with concentrations of tamoxifen and its metabolites in breast cancer patients.

BACKGROUND: Although tamoxifen (TAM) is the predominant adjuvant therapy for estrogen receptor positive (ER(+)) breast tumors, 50% of breast cancer patients do not respond positively to this therapy, or they experience adverse side effects. This variability in TAM responsiveness may be due to differences in TAM metabolism that stem from differences in race, age, and body mass index (BMI). Thus, the purpose of this study was to test the hypothesis that race, age, and BMI are associated with the metabolism of TAM to two primary metabolites, N-desmethyltamoxifen (N-DMT) and 4-hydroxytamoxifen (4-OHT). METHODS: The study design was cross-sectional, and data were analyzed using independent sample t tests and multiple linear regression models. Breast cancer patients (n = 99) taking TAM for at least 30 days were recruited from a local hospital clinic. Each participant provided informed consent, completed a questionnaire, and donated a blood sample. The questionnaire was used to ascertain race, age, and BMI. The blood samples were used to measure plasma concentrations of TAM, N-DMT, and 4-OHT. RESULTS: Plasma concentrations of TAM, N-DMT, and 4-OHT differed among individual patients. Age, but not race and BMI, was positively associated with plasma concentrations of TAM and N-DMT, even after adjustment for potential confounders (p = 0.02 for TAM and p = 0.03 for N-DMT). CONCLUSIONS: This study suggests that aging may alter the metabolism of TAM. As increased levels of TAM and TAM metabolites may provide a possible explanation for why older women taking TAM are at increased risk for adverse side effects, future studies should determine whether age-related differences in the concentrations of TAM and TAM metabolites are associated with differences in TAM toxicity or responsiveness.

Adult↗

PubMed2002

Current developments in LC-MS for pharmaceutical analysis.

The current developments in liquid chromatography-mass spectrometry (LC-MS) and its applications to the analysis of pharmaceuticals are reviewed. Various mass spectrometric techniques, including electrospray and nanospray ionization, atmospheric pressure chemical ionization and photoionization and their interface with liquid chromatographic techniques are described. These include high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography and the advantages and disadvantages of each technique are discussed. The applications of LC-MS to the studies of in vitro and in vivo drug metabolism, identification and characterization of impurities in pharmaceuticals, analysis of chiral impurities in drug substances and high-throughput LC-MS-MS systems for applications in the "accelerated drug discovery" process are described.

Chromatography, Liquid↗