Effects of boron neutron capture irradiation on the normal lung of rats.

The whole lung of rats was irradiated with X-rays, thermal neutrons, or thermal neutrons in the presence of p-boronophenylalanine (BPA). A >/= 20% increase in breathing rate, in the period 40-80 days after irradiation, was indicative of radiation-induced pneumonitis. The ED(50) (+/-SE) for a >/= 20% increase in breathing rate, relative to age-matched controls, was 11.6 +/- 0.13 Gy for X-rays and 9.6 +/- 0.08 Gy for neutrons only. This indicated a thermal neutron beam RBE of 1.2 and an RBE of 2.2 for the high-LET components of the dose, assuming a dose reduction factor of 1.0 for gamma rays. Preliminary data indicate the compound biological effectiveness factor for BPA in the lung is approximately 1.5.

Determination of guanfacine in biological fluids by electron-capture GLC.

A quantitative electron-capture GLC method with good sensitivity is described for the determination of guanfacine in human plasma and urine. By condensing its amidino group with hexafluoroacetylacetone, guanfacine is converted to a pyrimidino derivative with better GLC properties than the parent drug. This method allows the determination of guanfacine in plasma and urine at concentrations as low as 0.5 ng/ml and was applied successfully to measurement of plasma levels in humans after therapeutic dosing.

Drug interactions of the components of Optalidon after oral administration.

An investigation involving seven successive was undertaken on several groups of 10 to 14 volunteers, in order to evaluate any drug interaction between the three active components of Optalidon, namely amidopyrine (A), butalbital (B), and caffeine (C). Each component was investigated after oral administration, alone and in combination either with one of the others (i.e. A+B, B+C, C+A) or with both of the others in Optalidon (A+B+C). The plasma concentration and urinary excretion were recorded for each component as a function of time. For amidopyrine, two metabolites, amino-4-antipyrine and acetamino-4-antipyrine, were also measured in the urine. Based on a pharmacokinetic model, the following conclusions can be drawn: a) There is no change in bioavailability due to the combination of the three components in Optalidon in respect to their single administration. Within each study, there is no significant difference between the elimination rate constants, areas under the plasma concentration/time curve and percentage excreted in urine for the three components administered alone or in any combination with the other components of Optalidon. b) Concerning the absorption half-life, there is no change for amidopyrine. Only caffeine and butalbital show a statistically significant interaction in respect to this parameter and, as a consequence, differences in the time and value of the maximal plasma concentration in Optalidon. However, these differences are scarcely of anyl clinical relevance.

The effect of food and clopamide on the absorption of pindolol in man.

Plasma levels and urinary excretion of pindolol were measured in each of two groups of eleven subjects in order to compare the absorption of the drug when administered alone in the fasting state, and either with food or Binaldix. The data were analyzed according to a one-compartment model with first order absorption. No significant differences in absorption of pindolol were obtained in each study. Food appeared to increase the speed of absorption of pindolol leading to a slightly earlier and higher maximum plasma concentration, but this observation appears to be of no clinical relevance.