PubMed Health⌕ Search

Biomedical subjects

S Tett

Publications and source records attributed to S Tett.

9 recordsLinked to original sources
PubMed2001

Low tacrolimus concentrations and increased risk of early acute rejection in adult renal transplantation.

BACKGROUND: A retrospective analysis was performed on adult renal transplant recipients to evaluate the relationship between tacrolimus trough concentrations and the development of rejection in the first month after transplant. METHODS: A total of 349 concentrations from 29 patients, measured by enzyme-linked immunosorbent assay (ELISA), were recorded. Based on an increased serum creatinine, 12 patients were considered to have organ rejection. Rejection was confirmed by biopsy in five of these. The median trough concentration of tacrolimus over the first month of therapy, or until the time of first rejection was compared in rejecters vs non-rejecters. RESULTS: Median trough concentrations of tacrolimus were found to be lower in biopsy-proven rejecters vs non-rejecters (P=0.03) and all rejecters vs non-rejecters (P=0.04). The average median concentration (+/-SD) in the biopsy-proven rejecter group was 5.09+/-1.16 ng/ml, compared to 9.20+/-3.52 ng/ml in the non-rejecter group. After exclusion of an outlier, the average median concentration in all rejecters was 5.57+/-1.47 ng/ml, compared with 9.20+/-3.52 ng/ml in non-rejecters. A rejection rate of 55% was found for patients with a median trough concentration between 0 and 10 ng/ml. This compared with no observed rejection in patients with a median concentration between 10 and 15 ng/ml. CONCLUSION: A significant relationship exists between organ rejection and median tacrolimus trough concentrations in the first month post-transplant, with patients displaying low concentrations more likely to reject. In order to minimize rejection in the first month after renal transplantation, trough concentrations greater than 10 ng/ml must be achieved.

Acute Disease↗
PubMed1996

Hydroxychloroquine relative bioavailability: within subject reproducibility.

Six healthy volunteers received hydroxychloroquine sulphate 200 mg orally on four occasions (three tablets, one solution). Maximum hydroxychloroquine blood concentration (Cmax; range 135-422 ng ml-1) and time to maximum (tmax; range 1.5-7.0 h) for the three tablet doses showed significant differences between subjects (P < 0.009; between subject coefficients of variation (CVs) 34% and 27%, respectively). There were no within subject differences in Cmax (P = 0.32; mean within subject CV 11%), Cmax corrected for weight (P = 0.28) or tmax (P = 0.35; mean within subject CV 16%). Truncated areas under the hydroxychloroquine blood concentration-time curve of the three tablets were different between (P = 0.0001) but not within subjects (P = 0.13). Again, between subject CV (38%) was more than three times the mean within subject CV (12%). Bioavailability was not limited by tablet formulation. The significant variability in relative bioavailability between but not within individuals indicated that individualising dosing to target concentrations associated with optimal outcomes may minimise variability in response.

Adolescent↗
PubMed1995

Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection.

Fluconazole pharmacokinetics, including absolute bioavailability, were determined for one group of controls (n = 10) and two groups of people with human immunodeficiency virus (HIV) infection (those with CD4+ T-cell counts of less than [n = 4] or greater than [n = 9] 200 cells per mm3). Twenty subjects received four doses of fluconazole; three doses were oral (50, 100, and 400 mg), and one dose was intravenous (either 50, 100, or 400 mg). The other three subjects received one or two doses. The groups were comparable in terms of the weight, body mass index, and estimated creatinine clearance of the subjects, but the people with HIV infection were older. Pharmacokinetic parameters indicated linearity in all subjects; the area under the plasma concentration-time curve and the maximum concentration increased in proportion to the dose. The fraction of an oral dose of fluconazole absorbed approximated unity in all three groups of subjects. The mean (+/- standard deviation) plasma clearance of fluconazole was lowest in the group of subjects with low CD4+ T-cell counts; the value for this group was 0.74 +/- 0.19 liter/h, compared with 0.97 +/- 0.19 liter/h in the group with HIV infection and CD4+ T-cell counts of greater than 200 cells/mm3 and 1.18 +/- 0.23 liter/h in the group of control subjects (P < 0.05). The volume of distribution was lower in those with HIV infection (P = 0.04, corrected for weight). The half-life was longest in people with HIV infection and low CD4+ T-cell counts (P = 0.01). This study has shown that some differences do exist between the pharmacokinetics of fluconazole in people with HIV infection and those in noninfected controls.

Administration, Oral↗
PubMed1993

Who is ordering all those cyclosporin concentrations and how do they use them? An audit of cyclosporin therapeutic drug monitoring.

Therapeutic drug monitoring is used for the immunosuppressant drug, cyclosporin, even though it is often unclear what concentration should be targetted. At St. Vincent's Hospital, Sydney, a polyclonal, whole blood immunoassay is used to measure cyclosporin and metabolites. The objective of the present study was to audit how the concentration results produced by the laboratory were actually used to adjust dosage. Each transplantation unit was asked about their policy for dosage adjustment and which therapeutic range was used. The audit criteria were considered to be passed if the action taken based on a concentration result was (a) predictable based solely on the concentration and its relationship to the stated therapeutic range (e.g., dosage increased if concentration was below therapeutic range) or (b) based on clinical considerations (e.g., dosage decreased because of increased serum creatinine). Data were collected for the actions taken following 347 concentration results over a 6-week period. Audit criteria were fulfilled for 246 (71%) of the results. The majority of the cyclosporin concentrations (75%) were determined for the cardiopulmonary unit; 66% of these fulfilled audit criteria. Approximately two-thirds of all the cyclosporin concentrations requested were followed up by appropriate action based on stated therapeutic ranges or documented clinical reasons.

Cyclosporine↗
PubMed1993

Insights from pharmacokinetic and pharmacodynamic studies of hydroxychloroquine.

There is wide variability between subjects in the pharmacokinetic parameters of hydroxychloroquine. A range of concentrations is achieved by individuals receiving the same dosage. In a cross-sectional study, mean hydroxychloroquine concentrations in patients with shorter duration and lower intensity of morning stiffness and no rheumatoid factor were significantly higher than in patients with worse disease activity. Variable kinetic parameters, causing variable concentrations, are likely to be contributing to the variability in response to hydroxychloroquine in rheumatic diseases.

Adult↗
PubMed1992

Multiple medication use in the elderly. Use of prescription and non-prescription drugs in an Australian community setting.

OBJECTIVE: To document the extent of polypharmacy or multiple medication use in the elderly. DESIGN: Cross-sectional examination of an age cohort of a community. SETTING: Community-based study in Dubbo, NSW, in 1988-1989. SUBJECTS: All non-institutionalised residents aged 60 years and over, numbering 1237 men and 1568 women. MAIN OUTCOME MEASURES: Assessment of use of prescription and non-prescription drugs, recent hospitalisation, years of education, psychosocial variables. RESULTS: 18% of men and 25% of women were currently using three or more classes of prescription drugs. The corresponding values for two or more classes of non-prescription drugs were 29% and 44%. Of those who were using multiple prescription drugs 56% of men and 76% of women were also using multiple non-prescription drugs. In a multiple logistic model, the following possible predictors of multiple drug use were included: hospitalisation in the last six months, age, sex, depression, life satisfaction and education. Multiple prescription drug use was significantly predicted by recent hospitalisation (odds ratio [OR] = 2.40; 95% confidence interval [CI], 1.63-3.56), increasing age (e.g. 70-79 years versus 60-69 years; OR = 2.54; CI, 1.97-3.25), female sex (OR = 1.59; CI, 1.25-2.01) and increasing depression (e.g. highest tertile of depression scale versus lowest; OR = 2.52; CI, 1.84-3.42). Multiple non-prescription drug use was significantly predicted by female sex (OR = 2.38; CI, 1.95-2.92) and increasing depression (OR = 2.77; CI, 2.16-3.56). For prescription items, non-prescription items, and both categories in combination levels of use 20% above the population average have been documented. CONCLUSIONS: Polypharmacy in the elderly population appears to be predicted by recent hospitalisation, increasing age, female sex and increasing depression. There is potential for drug-drug interaction to occur, but the findings suggest target areas for preventive action.

Aged↗
PubMed1990

Antimalarials in rheumatic diseases.

The antimalarials hydroxychloroquine and chloroquine remain established and effective agents for the treatment of rheumatoid arthritis and systemic lupus erythematosus. Although the mechanisms of action remain uncertain, evidence is accumulating that the antirheumatic and immunological effects of the antimalarials are related to their massive distribution into the cellular acid-vesicle system. These drugs are attracting new interest because their relative safety recommends their use in early rheumatoid arthritis and as a component of second-line antirheumatic drug combinations. The absence of data examining the effect of antimalarials upon radiological progression of rheumatoid arthritis needs to be rectified. Recent understanding of the pharmacokinetics of these drugs reveals that steady-state concentrations are not achieved for at least 3-4 months. Preliminary information also suggests a relationship between blood concentrations and effect. Taken together, these data suggest that more effective dosage regimens will be possible when therapeutic concentration ranges are properly established.

Antimalarials↗