• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.245-251
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• 2016

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) ($23{\times}ABW^{0.5}mg\;daily$) targeting an area under the concentration-time curve (AUC) of $5924{\mu}M{\cdot}min$. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC ($AUC_{PRED}$). The accuracy and precision of the $AUC_{PRED}$ values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of $5924{\mu}M{\cdot}min$. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of $AUC_{PRED}$ were -5.8% and 20.6%, respectively, in the conventional dosing group and -2.1% and 14.0%, respectively, in the new dosing scheme group. These findings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.

• Journal of Life Science
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• v.25 no.5
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• pp.533-538
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• 2015

Four sites and one site were used to analyze fish diversity at the water systems of the Sineun reservoir and the Jeonchon reservoir, respectively. The field experiments were conducted to test the density dependence that could lead to population regulation by artificial inferences and environmental changes. We examined the effects of environmental factors on fish densities using SMATR freeware. It was estimated to be reduced to the density effect at four sites in 2012. Shannon-Weaver indices of the diversity (H’) of the Sineun reservoir were similar to those of the Jeonchon reservoir. Species diversity was in a range of 0.645 to 2.105. The H’ value of the upper region was higher than those of middle and low regions were, and values of richness were lower in downstream than upstream. Using the maximum likelihood solution for the removal estimators of two low regions of the river stations, the estimated migration probabilities from the resident fish to the migrated fish for five species (Cyprinus cuvieri, Carassius auratus, Pseudorasbora parva, Misgurnus mizolepis, and Oryzias latipes) had a mean of 0.623. Especially, migration probabilities from the Jeonchon reservoir to the Sineun reservoir for five species were high (a mean of 0.681). The period of migration was suggested to be about one month because of short geographical distances (50 m). We found no significant difference between the three categories in the distribution of the other four species, indicating the species probability was similar among stations.