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1.
Pharmaceutics ; 14(3)2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35336021

ABSTRACT

We develop a population pharmacokinetic model to describe Busulfan pharmacokinetics in paediatric patients and investigate by simulations the impact of various sampling schedules on the calculation of AUC. Seventy-six children had 2 h infusions every 6 h. A two-compartment linear model was found to adequately describe the data. A lag-time was introduced to account for the delay of the administration of the drug through the infusion pump. The mean values of clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 10.7 L/h, 39.5 L, 4.68 L/h and 17.5 L, respectively, normalized for a Body Weight (BW) of 70 kg. BW was found to explain a portion of variability with an allometric relationship and fixed exponents of 0.75 on clearance parameters and 1 on volumes. Interindividual variability for clearance and volume of distribution was found to be 28% and 41%, respectively, and interoccasion variability for clearance was found to be 11%. Three sampling schedules were assessed by simulations for bias and imprecision to calculate AUC by a non-compartmental and a model-based method. The latter was found to be superior in all cases, while the non-compartmental was unbiased only in sampling up to 12 h corresponding to a once-daily dosing regimen.

2.
Pediatr Transplant ; 26(4): e14239, 2022 06.
Article in English | MEDLINE | ID: mdl-35122456

ABSTRACT

BACKGROUND: Infants are subjected to hematopoietic stem cell transplantation (HSCT) due to malignant and non-malignant diseases. However, specific data concerning the outcome and transplantation-related complications in infants, as a separate age group, are limited. Our aim was to evaluate the impact of infancy on the outcome, toxicity, and complications after HSCT. METHODS: We retrospectively analyzed data of 55 infants that underwent HSCT in our unit from May 1997 until February 2020, emphasizing on the probability of overall survival (OS) and the cumulative incidence (CI) of transplantation-related mortality (TRM) and complications. RESULTS: We report a probability of OS of 61%, a CI of TRM at day 100 and 365 post transplantation of 22% and 30%, respectively, and additionally a CI of graft failure, acute graft-versus-host disease (GvHD), and infectious complications, 18%, 44%, and 39%, respectively. No statistically significant association was detected between the above mentioned parameters and diagnosis, the use of myeloablative or non-myeloablative/reduced toxicity conditioning regimens or the type of donor. CONCLUSIONS: We conclude that HSCT in infancy is associated with significant mortality and morbidity. This is possibly attributed to endogenous, age-related factors. More specifically, infants may be at a higher risk of toxicities due to the immaturity of developing vital organs and the deficiency of the newly adopted immune system that predisposes them to infectious complications. The development of GvHD further augments the danger of infections, in a potential vice-versa relationship. Moreover, there are few data on pharmacokinetics of chemotherapy agents, making safe and efficacious drug administration hard.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Morbidity , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation Conditioning/adverse effects
4.
Antimicrob Agents Chemother ; 60(1): 632-6, 2016 01.
Article in English | MEDLINE | ID: mdl-26503649

ABSTRACT

Voriconazole levels were determined with high-performance liquid chromatography (HPLC) and a microbiological agar diffusion assay using a Candida parapsilosis isolate in 103 serum samples from an HPLC-tested external quality control program (n = 39), 21 patients receiving voriconazole monotherapy (n = 39), and 7 patients receiving combination therapy (n = 25). The results of the bioassay were correlated with the results obtained from the external quality control program samples and with the HPLC results in sera from patients on voriconazole monotherapy and on combination therapy with an echinocandin (Spearman's rank correlation coefficient [rs], > 0.93; mean ± standard error of the mean [SEM] % difference, <12% ± 3.8%).


Subject(s)
Antifungal Agents/blood , Biological Assay , Candidiasis/drug therapy , Echinocandins/administration & dosage , Voriconazole/blood , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacokinetics , Candida/drug effects , Candida/growth & development , Candidiasis/blood , Candidiasis/microbiology , Chromatography, High Pressure Liquid , Colony Count, Microbial , Drug Therapy, Combination , Humans , Quality Control , Regression Analysis , Reproducibility of Results , Sensitivity and Specificity , Voriconazole/administration & dosage , Voriconazole/pharmacokinetics
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