Biomedical subjects

Joaquim Figueiredo

Publications and source records attributed to Joaquim Figueiredo.

4 recordsLinked to original sources

PubMed2002

Differential influence of two cyclosporine formulations on everolimus pharmacokinetics: a clinically relevant pharmacokinetic interaction.

Everolimus is an immunosuppressant intended for use with cyclosporine in acute-rejection prophylaxis following organ transplantation. The possibility of a drug interaction of cyclosporine on everolimus was assessed. In this randomized, two-period, crossover study, 24 healthy subjects received a single oral dose of 2 mg everolimus alone and with one of two cyclosporine formulations: either 175 mg Neoral or 300 mg Sandimmune. The single doses of Neoral and Sandimmune were chosen to yield similar average areas under the concentration-time curve (AUC). Treatments were separated by a 14-day washout period. Cyclosporine AUCs were similar for both formulations (p = 0.53), whereas the peak concentration (Cmax) was significantly higher for Neoral (p = 0.02). Simultaneous administration of Neoral with everolimus increased everolimus Cmax and AUC by 82% and 168%, respectively (p = 0.0001). Coadministration of Sandimmune with everolimus did not affect everolimus Cmax (p = 0.59) but increased everolimus AUC by 74% on average (p = 0.0001). Everolimus elimination half-lives were unchanged in the presence of both cyclosporine formulations. The everolimus AUC increase with Neoral coadministration was significantly greater than the AUC increase with Sandimmune (p = 0.008). However, there was no apparent association between cyclosporine Cmax and the change in everolimus AUC with cyclosporine coadministration. If Neoral or Sandimmune is removed from an everolimus-cyclosporine immunosuppressive regimen, a two- to three-fold decrease in everolimus exposure is expected. Therapeutic monitoring of everolimus concentrations would be helpful after the removal of cyclosporine to individually titrate everolimus exposure.

Adult↗

PubMed2002

Effect of rifampin on apparent clearance of everolimus.

OBJECTIVE: To assess the influence of the CYP3A4 enzyme inducer rifampin on the pharmacokinetics of the immunosuppressant everolimus to provide guidance for their coadministration. METHODS: In this open-label, single-sequence, crossover study, 12 healthy subjects received a single oral 4-mg dose of everolimus alone and again after an 8-day pretreatment with rifampin 600 mg/d. Urinary excretion of 6beta-hydroxycortisol was measured at various time points during rifampin treatment as a marker of CYP3A4 induction. RESULTS: Urine excretion of 6beta-hydroxycortisol was significantly elevated during treatment with rifampin compared with prestudy, indicating enzyme induction. When everolimus was coadministered during rifampin treatment, the apparent clearance of everolimus was significantly increased, on average by 172%. This was manifested as a decrease in maximum concentration in all subjects, on average by 58% (range 14-73%). The AUC remained unaffected in 1 subject (although 6beta-hydroxycortisol indicated enzyme induction) and decreased in the other 11 subjects. The average decrease in AUC in the full study population was 63% (range 0-82%). Everolimus half-life was reduced significantly, from an average of 32 hours to 24 hours. CONCLUSIONS: In everolimus-treated patients for whom rifampin is indicated, alternative agents with less enzyme induction potential than rifampin could be considered. Alternatively, the dose of everolimus could be individually titrated based on everolimus therapeutic drug monitoring during rifampin therapy.

Adult↗

PubMed2002

Effect of food on everolimus absorption: quantification in healthy subjects and a confirmatory screening in patients with renal transplants.

STUDY OBJECTIVE: To quantify the influence of a high-fat meal on the oral bioavailability of the immunosuppressant everolimus in a single-dose study in healthy subjects and to confirm the results in a small food-effect screening assessment in patients with renal transplants who were receiving multiple-dose everolimus. DESIGN: Randomized, open-label, crossover, single-dose study and confirmatory screening. SETTING: Phase 1 unit for the single-dose study and two German hospitals for the patient screening. SUBJECTS: Twenty-four healthy male volunteers; six clinically stable patients with renal transplants who were originally part of a phase I dose-escalation study. INTERVENTION: The 24 healthy men received everolimus 2 mg orally under fasting conditions and after a high-fat meal. The six patients received everolimus 2.5 mg/day orally, in addition to cyclosporine and prednisone. On two occasions, a pharmacokinetic profile was obtained over the dosing interval after drug administration under fasting conditions and after a high-fat meal in a randomized sequence. MEASUREMENTS AND MAIN RESULTS: In the single-dose study in healthy subjects, a high-fat meal delayed everolimus time to maximum concentration (Tmax) by a median 1.25 hours, reduced peak blood concentration (Cmax) by 60%, and reduced area under the concentration-time curve (AUC) by 16%. In the multiple-dose screening in patients with renal transplants, a high-fat meal delayed Tmax by a median 1.75 hours and reduced Cmax by 53% and AUC by 21%. Everolimus trough levels showed no food effect, whereas the peak-trough fluctuation was dampened by 52%. CONCLUSIONS: A high-fat meal modestly reduced everolimus AUC. To minimize longitudinal variability in exposure, everolimus should be administered consistently either with food or without food.

Administration, Oral↗

PubMedDate not supplied

Full-face undermining using progressive dilators.

The application of a new and simple method of facial cutaneous detachment using specially designed bifaceted rigid steel wands called Dilson Luz Vascular Dilation Wands is described. These wands considerably reduce the bleeding during face-lift surgery, reducing both postoperative hematomas and the risk of facial nerve injury. This technique involves stretching the blood vessels to the point of rupture by inserting progressively larger wands. At the point of rupture, a spontaneous coagulation within the vascular extremities occurs. This is attributable to a significant blood platelet migration induced by the stimulation from the rupture of the vascular intima. The wands, varying in dimension from 1.5 to 20 mm, and are used for cutaneous facial detachment. This method has been found to result in minimal bleeding across the detached surface as well as an excellent perfusion of the overlying skin. With the use of these Dilson Luz Vascular Dilation Wands in combination with this new technique, the authors have obtained improved cutaneous detachment; reduced postoperative swelling, edema, and ecchymosis; prophylaxis of facial nerve damage; reduced procedural time; and above all, greater reduction in immediate and late postoperative hematoma formation.

Adult↗