Simvastatin (SV), a HMG-CoA reductase inhibitor, is widely used for the treatment of hyperlipidaemia. The objectives of the present study were to develop a population pharmacokinetic-pharmacodynamic (PK-PD) model for simvastatin and to evaluate its usefulness in predicting the dose-response relationship of simvastatin in patients with hyperlipidaemia. The data were obtained from a drug-drug interaction study to assess the effect of aspirin on the PK of simvastatin. Twenty-seven healthy volunteers were given simvastatin 40 mg daily for 14 days in whom aspirin 100 mg q.d. was co-administered after day 8. Full PK studies were performed on days 1, 7 and 14 in addition to trough sampling on days 5, 6, 12 and 13. Low-density lipoprotein-cholesterol (LDL-C) levels were also measured serially. Then, a population PK-PD model for simvastatin and its active metabolite, simvastatin acid (SVA), was developed using mixed effect methods (NONMEM Ver. 6.2). A simple linear PK model with parent and metabolite compartments provided the best fit for the 2647 concentrations of simvastatin and sim-vastatin acid, and a turnover model was used to describe the change in LDL-C levels. The dose-response curve simulated from the final model and those obtained from the literature overlapped very closely. No influence of aspirin was observed in PK or PD. A simple PK-PD model developed using only 2-week study data from fewer than 30 healthy volunteers successfully predicted the dose-response relationship of simvastatin in patients when compared with published data. Simvastatin (SV) is a HMG-CoA reductase inhibitor effective in the treatment of hypercholesterolaemia and hypertri-glyceridaemia [1]. It is widely used to reduce the risk of cardiovascular morbidity and mortality [2] and thromboem-bolic stroke in high-risk patients [3,4]. After oral administration , simvastatin is rapidly absorbed (t max of 1-2 hr) [5,6] and eliminated. Less than 10% of the peak HMG-CoA reductase inhibitory activity remains after 12 hr (t 1 ⁄ 2 = 2-5 hr) [5,7]. Once administered, simvastatin rapidly undergoes reversible non-enzymatic or carboxylesterase-mediated conversion to its active metabolite, simvastatin acid (SVA), in the liver, intestinal mucosa and plasma [1,8]. CYP450 is also known to metabolize a small fraction of simvastatin. Simvastatin acid prevents HMG-CoA reductase from converting HMG-CoA to mevalonate, which is a rate-limiting step in cholesterol biosynthesis [9]. Inhibition of the HMG-CoA reductase in the liver results in the reduction in cholesterol synthesis. Moreover, the up-regulation of low-density lipoprotein (LDL) receptors located on the cell membranes of the liver and extrahepatic tissues thereby also contributes to the reduction in plasma LDL-cholesterol (LDL-C) concentrations [10]. There are many reports on the safety, efficacy and metabolism of simvastatin. To date, there have been no published population pharmacokinetic-pharmacodynamic (PK-PD) models for simvastatin or simvastatin acid. Recently, we performed a drug-drug interaction s...

Both glucosamine and cyclosporin have been reported to show immunomodulatory effect with inhibition of each different key transcription factor for cytokine gene expression and T-cell function. The overall purpose of this pilot study was to assess the feasibility of the combination of cyclosporin with glucosamine for the treatment of patients with atopic dermatitis. Twelve patients more than 12 years old who required systemic cyclosporin were included in the study. Two of them dropped out due to violation of medication schedule. The single (S) and combination (C) regimens were crossed over every 2 weeks without a washout period between the cross-over for 6 months. Five patients were randomly assigned to the S regimen first (SC sequence), whereas the other five were given the C first (CS sequence). The change of SCORAD index was analyzed as the primary efficacy end-point by general linear model and piecewise linear mixed model. The SCORAD index was reduced with both SC and CS sequence regimens. In particular, index reduction with the C was more than that associated with S regimen; this difference increased as time lapsed. The glucosamine combination was predicted to cause an additive decrease in the mean percent change of the SCORAD index (~6%), with decreasing interleukin (IL)-4 and IL-5 cytokine levels but without increasing treatment-related adverse events. This study suggests that the C would produce better clinical outcomes than the S regimen in patients with atopic dermatitis, although confirmatory clinical trials are warranted to determine the effect of combination.

MTS increased collagen deposition more than IPL, and MTS might be more effective than IPL for scar treatment. The authors have indicated no significant interest with commercial supporters.

PurposeThe present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (Ctrough) and microorganism-specific (AUC24/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever.Materials and MethodsOne thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC24/MIC >125 [or 345] using logistic analysis.ResultsThe standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L, respectively.ConclusionThe current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered.

Our data showed that the mean placental transfer of clarithromycin is approximately 8% and dependent on gestational age.