An estimation method of the half-life for a one-compartment model of a single bolus intravenous injection by a single sampling.

In clinical trials, sometimes only a single drug concentration can be measured from a patient because of the patient's burden. In this case, the sampling point is usually identical for all patients. From a single concentration, we cannot generally obtain point-estimates of each pharmacokinetic parameter.

A note on post-marketing safety study design to characterise time-dependent adverse events.

Purpose: To investigate a suitable post-marketing safety study design, that is number of patients and duration of exposure, to well characterise adverse events (AEs) profiles under limited resources, fixed patient-months.

Methods: A simulation study is conducted to investigate a suitable study design that can appropriately characterise the shape of the hazard function of AEs using the Weibull model. The reliability of the estimates is evaluated by referring their bias and mean squared error (MSE).

Treatment of thoracic esophageal carcinoma invading adjacent structures.

T4 esophageal cancer is defined as the tumor invading adjacent structures, using tumor-node-metastasis (TNM) staging. For clinically T4 thoracic esophageal carcinoma, multimodality therapy, that is, neoadjuvant chemoradiotherapy (CRT) followed by surgery or definitive CRT, has generally been performed. However, the prognosis of patients with these tumors remains poor.

Profile likelihood-based confidence intervals using Monte Carlo integration for population pharmacokinetic parameters.

Population pharmacokinetic (PPK) analysis usually employs nonlinear mixed effects models using first-order linearization methods. It is well known that linearization methods do not always perform well in actual situations. To avoid linearization, the Monte Carlo integration method has been proposed.

Extended information criterion (EIC) approach for linear mixed effects models under restricted maximum likelihood (REML) estimation.

In clinical data analysis, the restricted maximum likelihood (REML) method has been commonly used for estimating variance components in the linear mixed effects model. Under the REML estimation, however, it is not straightforward to compare several linear mixed effects models with different mean and covariance structures. In particular, few approaches have been proposed for the comparison of linear mixed effects models with different mean structures under the REML estimation.

A note on population pharmacokinetic studies with a single sampling design.

The choice of sampling time point in a population pharmacokinetic study with severe limitation on the number of samples per study subject (single sampling design) is critical in obtaining reliable parameter estimates. The authors have investigated the relationship between the timing as well as the degree of distribution of a sampling point among study subjects and the reliability of the estimates of pharmacokinetic parameters in a population pharmacokinetic study. This was achieved through a simulation, assuming an intravenously administered drug whose pharmacokinetic profile follows a 1-compartment model.

Evaluation of Bayesian estimation of pharmacokinetic parameters.

The validity of pharmacokinetic parameters estimated by the maximum a posteriori probability (MAP) Bayesian method was investigated by simulation studies. A 1-compartment model with bolus intravenous administration was used as a pharmacokinetic model, and the coefficients of variation for the parameters and residual error were set at 30% and 10%, respectively. The accuracy of the posterior modes of pharmacokinetic parameters estimated by the MAP Bayesian method was assessed by the difference between the true value and the estimated value.

Observation of time-dependent adverse events and the influence of drop-out thereon in long-term safety studies--simulation study under the current practice of post-marketing safety evaluation in Japan.

Safety assessment of a new drug should be continuously carried out in the premarketing phase as well as in the postmarketing phase. Considering the actual conditions and problems of postmarketing safety studies in Japan, i.e.

A simulation-based confidence band for drug concentrations in blood: an application to a clinical phase I trial.

Since drug concentrations in blood are usually related to the effectiveness and toxicity, a confidence band for the drug concentrations gives useful information for the treatment. This paper proposes a simulation-based approach for constructing confidence bands for drug concentrations in blood. The confidence band covers the whole profile of the drug concentrations with a specified probability.

An experimental study of jejunal pouch replacements following total gastrectomy.

Background/aims: The nutritional effects of pouch replacement after total gastrectomy remain clinically controversial. Two previous experiments failed to show any nutritional benefit. However, the pouches applied clinically and examined experimentally so far were all of anti-peristaltic type.

Penetration of Pazufloxacin into the Fluid of Suction Blisters Induced in Human Skin.

We investigated the pharmacokinetics of pazufloxacin (PZFX) in the fluid of suction blisters induced in the skin of 6 healthy male volunteers after a 200mg oral dose of PZFX. The time to reach the maximum concentration (t) of PZFX in plasma was 0.7 hours, and the maximum concentration (C) was 2.