Therapeutic drug monitoring
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Randomized Controlled Trial
A limited sampling strategy for estimating individual pharmacokinetic parameters of coagulation factor VIII in patients with hemophilia A.
Therapeutic drug monitoring of factor VIII is well established in the treatment of patients with hemophilia attributable to important interindividual variability. The individual initial factor VIII dosage is usually calculated according to individual pharmacokinetic parameters obtained after a dose test administered before the surgery, using at least five-concentration data. The authors proposed a limited sampling strategy to estimate individual pharmacokinetic parameters from one- or two-concentration data in patients with hemophilia A before surgery. ⋯ No information was given on the bias and precision of the estimation. This paper reports a one-stage method for a population pharmacokinetic study of factor VIII. The Bayesian estimation of individual pharmacokinetic parameters based on only two sampling times (0.5 and 6 hours or 0.5 and 8 hours after the end of infusion) is useful to define the best factor VIII dosage in hemophilic patients before surgery.
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Clinical Trial
Safety of 96-hour incision-site continuous infusion of ropivacaine for postoperative analgesia after bowel cancer resection.
The aim of this study was to examine the safety of ropivacaine given to patients as a continuous infusion [0.2% (2 mg/mL), 5 mL/h for 96 hours] into a right lateral transverse incision using a portable elastomeric infusion pump after colon cancer resection. Blood samples were collected throughout the infusion and up to 12 hours after infusion and were analyzed by high-performance liquid chromatography (HPLC) for total and unbound ropivacaine concentrations in plasma. Alpha1 acid glycoprotein (AAG) concentrations were measured at 0 and 48 hours to assess possible changes in ropivacaine protein binding after surgery. ⋯ No signs or symptoms of ropivacaine toxicity were observed or reported on questioning. In this limited sample, extending the infusion period from the presently approved 48 hours to 96 hours seems to be a safe alternative and/or adjunct to standard opiate analgesia after colorectal surgery using a right lateral transverse incision, hence reducing the incidence of opiate adverse effects and enhancing recovery. Unbound ropivacaine concentrations suggest there is scope for testing elevated doses to enhance efficacy further.
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Clinical Trial
Population pharmacokinetics and bayesian estimator of cyclosporine in pediatric renal transplant patients.
Cyclosporine A (CsA) is an immunosuppressive drug widely used in pediatric renal graft recipients. Its large interindividual pharmacokinetic variability and narrow therapeutic index render therapeutic drug monitoring necessary. However, information about CsA pharmacokinetics is scarce and no population pharmacokinetic (popPK) studies in these populations have been reported so far. to the objectives of this study were 1) to develop a PKpop model and identify the individual factors influencing the variability of CsA pharmacokinetics in pediatric kidney recipients; and 2) to build a Bayesian estimator allowing the estimation of the main PK parameters and exposure indices to CsA on the basis of a limited sampling strategy (LSS). ⋯ This article reports the first popPK study of CsA in pediatric renal transplant patients. It confirms the reliability and feasibility of CsA AUC estimation in this population. The body weight and the posttransplantation delay were identified to influence PK interindividual variability of CsA and were included in the Bayesian estimator developed, which could be helpful in further clinical trials.
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Randomized Controlled Trial Multicenter Study
Pharmacokinetics of digoxin cross-reacting substances in patients with acute yellow Oleander (Thevetia peruviana) poisoning, including the effect of activated charcoal.
Intentional self-poisonings with seeds from the yellow oleander tree (Thevetia peruviana) are widely reported. Activated charcoal has been suggested to benefit patients with yellow oleander poisoning by reducing absorption and/or facilitating elimination. Two recent randomized controlled trials (RCTs) assessing the efficacy of activated charcoal yielded conflicting outcomes in terms of mortality. ⋯ This effect was approximately equal in patients administered MDAC or SDAC. Activated charcoal appears to favorably influence the pharmacokinetic profile of Thevetia cardenolides in patients with acute self-poisoning and may have clinical benefits. Given the conflicting clinical outcomes noted in previous RCTs, these mechanistic data support the need for further studies to determine whether a particular subgroup of patients (eg, those presenting soon after poisoning) will benefit from activated charcoal.
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Dihydropyrimidine dehydrogenase (DPD) deficiency leads to dramatic overexposure to fluorouracil (5-FU), resulting in a potentially lethal outcome in patients treated with standard doses. The aim of this study was to validate, in a routine clinical setting, a simple and rapid method to determine the DPD status in a subset of cancer patients, all presenting with life-threatening toxicities following 5-FU or capecitabine intake. In this study, 80 out of 615 patients (13%) suffered severe toxicities, including 5 lethal ones (0.8%), during or after chemotherapy with a fluoropyrimidine drug. ⋯ Importantly, no IVS14+1G>A mutation was found in these patients, including those displaying the most severe or lethal toxicities. These data warrant systematic detection of DPD-deficient patients prior to fluoropyrimidine administration, including when oral capecitabine (Xeloda) is scheduled. Finally, the simplified methodology presented here proved to be a low cost and rapid way to identify routinely patients at risk of toxicity with 5-FU or capecitabine.