The impact of the concentration of drug binding plasma proteins on drug distribution according to Øie-Tozer's model.

1. New equations have been developed from an updated version of Øie-Tozer's model expressing how the free concentration and volume of distribution change in relation to changes in the concentration of drug binding plasma proteins. This updated model accommodates more than one drug binding plasma protein to contribute to the plasma protein binding. 2. Demonstrations of the model show that variability in the concentration of one plasma protein has considerably less impact on the free drug concentration and volume of distribution if other plasma proteins contribute to binding, than if they don't.

Visualization of plasma and tissue binding using dose fractions parameter.

A novel concept of dose fractions, based on the distribution of total bioavailable dose between the six combinations of location and binding state in Øie-Tozer's model is suggested as a way to visualize the distribution pharmacokinetics of a drug. The concept of dose fractions provides a sharper terminology in discussions of drug distribution allowing for a more precise description of the state and location of a drug within a system. In medicinal chemistry literature, the free fraction of a drug in plasma is a commonly discussed factor affecting the exposure to free drug while tissue binding is less well addressed. The free dose fraction, defined as the fraction of the bioavailable dose existing in free form, is suggested as a potentially valuable term for such discussions. Presently, drugs with high (>95%) plasma protein binding are viewed with skepticism, the rational behind which is questioned. The plasma protein bound dose fraction defined as the fraction of the total available dose, which is bound to plasma proteins, is suggested as a measure of the risk for problems related to fluctuations in free drug exposure due to variations in the concentration of drug binding plasma protein.

Postoperative brachytherapy and electron beam irradiation for keloids: A single institution retrospective analysis.

The aim of the present study was to perform a retrospective analysis of the control rate and toxicity of postoperative brachytherapy and electron beam irradiation for keloids. A retrospective review was performed of 116 keloid patients who underwent postoperative brachytherapy and electron beam irradiation between January 1, 2002 and June 30, 2012. Several different radiotherapy techniques and fractionation schedules were performed in the analysis, including high-dose rate (HDR) irradiation with 192Ir at 8 Gy/1 fraction (F)+9 Gy/3F or 20 Gy/4F; HDR brachytherapy with 60Co at 20 Gy/4F or 18 Gy/6F; or external beam electron therapy at 26 Gy/13F or 30 Gy/15F. The endpoints of the study were analysis of the control rate and toxicity. The median observation period was 46.5 months (range, 10.0-120.0 months) for all patients. In total, 18 of the 116 patients relapsed, and 16.7 months (range, 10.0-30.0 months) was the median time to recurrence for these patients. The control rates for the patients who received hypofractionation (>2 Gy per fraction) and conventional fraction (2 Gy per fraction) were 88.5 and 76.3%, respectively (P=0.043). The control rates for the patients whose calculated biological effective doses (BED) were >30 Gy and <30 Gy were 89.7 and 79.3%, respectively (P=0.104). There were no grade 2 or higher adverse effects based on the Common Terminology Criteria for Adverse Events v3.0 in the late phase. No evidence was identified for a link between radiotherapy and the subsequent occurrence of cancer. The results of the present study indicate that hypofractionated radiotherapy played an important role as an adjuvant therapy following surgical excision of keloids. A BED of >30 Gy appears to be sufficient. No definitive evidence was found for an association between radiotherapy and the occurrence of cancer during the follow-up, however, more cases and longer follow-up periods are required.