J. H. Glerum

Responders and non-responders after fluoride therapy in osteoporosis

Patients with osteoporosis were treated for two years with sodium fluoride. Fifteen received sodium fluoride in capsules, 56 in enteric coated slow release tablets (Ossin) and 20 in enteric coated tablets (Procal). Seven women treated with Procal were also treated with oestrogens. All patients had a calcium intake between 1000 and 2000 mg/day, used dihydrotachysterol for vitamin suppletion and were advised to exercise. Non-responders were arbitrarily defined as those who had an increase in serum alkaline phosphatase less than 10 U/l, those who had no increase in bone mineral content measured with CT in L4 and those who got a femoral neck fracture during the period of therapy. In the overall group of 91 patients 20% were non-responders based on a serum alkaline phosphatase increase less than 10 U/l. Based on the changes in bone mineral content 40% were non-responders during the first year of treatment, 45% during the second year and 23% over the first plus second year. The impression is that patients with a femoral neck fracture have a higher increase in serum parathyroid hormone concentration than patients without fractures. The urinary excretion of fluoride has a better predictive value than the change in serum alkaline phosphatase concentration for the prediction of an increase in bone mineral content.

In Vitro Binding characteristics for cesium of two qualities of prussian blue, activated charcoal and Resonium-A

The in vitro binding characteristics of radioactive 137Cs to two forms of Prussian blue [colloidally (soluble) K3Fe[Fe(CN)6] and insoluble Fe4[Fe(CN)6]3] and to activated charcoal and sodium polystyrene sulfonate (Resonium-A) were investigated by constructing Langmuir isotherms at pH = 1.0, 6.5 and 7.5 at 37 degrees C. At the three pHs investigated, 137Cs binding to activated charcoal and sodium polystyrene sulfonate was negligible. Binding of 137Cs to insoluble Prussian blue exceeded that for the soluble form and was pH dependent for both formulations. Maximum binding capacities were 87 mg/g (pH = 1.0), 194 mg/g (pH = 6.5) and 238 mg/g (pH = 7.5) for the insoluble form and 48 (pH = 1.0), 73 (pH = 6.5) and 78 (pH = 7.5) for the soluble form. As activated charcoal did not bind 137Cs, charcoal hemoperfusion is of no value. This has been confirmed by an in vitro experiment, using a Gambro Adsorbs 300 C cartridge.

Absolute bioavailability of fluoride from disodium monofluorophosphate and enteric-coated sodium fluoride tablets

Objectives: The absolute bioavailability and other pharmacokinetic parameters of two fluoride formulations were investigated in 13 healthy volunteers, aged 61–70 years.Methods:The following formulations were administered, under fasting conditions, in a single-dose three-way cross-over design: tablets of 76 mg disodium monofluoro phosphate (MFP, equivalent to 10.0 mg F− ion), enteric-coated (e.c.) tablets of 25 mg sodium fluoride (NaFor, equivalent of 11.3 mg F− ion), and an isoosmotic aqueous injection solution (4 ml) of 22.1 mg sodium fluoride (NaFiv, equivalent of 10.0 mg F− ion). There was a wash-out period of at least one week between each administration. Blood was sampled before and during a 24-hour period after administration. For F− excretion urine was sampled 48 hours before (baseline) and over the 48 hours after the adminstration.Results:The mean t1/2 values of the three formulations were 8.3, 8.7 and 8.3 h for MFP, NaFor and NaFiv respectively, and were not significant different. Mean Cmax after MFP was significantly higher than after NaFor [344 vs 142 μg⋅l−1]. Mean tmax for MFP was shorter than for NaFor [1.1 vs 4.6 h]. MFP had significantly higher bioavailability [102.8%] than NaFor [64.2%].Conclusion:The MFP formulation showed higher bioavailability with smaller variation than the NaFor formulation. MFP is preferable, therefore, for fluoride therapy in clinical practice, and changing from NaFor to MFP will require adjustment of the dose.

A new and improved gas chromatographic method for the determination of fluoride in plasma and faeces.

A method is described that extracts fluoride selectively as trimethylfluorosilane using carbon tetrachloride and trimethylchlorosilane. Drawbacks of other methods as well as advantages of the proposed method are discussed.The method is directly applicable to plasma and faeces samples, has a short gas Chromatographic run time due to the use of a backflush technique and is suitable for automation. Its lowest quantifiable limit for plasma and faeces is 10 μg/l and 1 μg/g fluoride respectively, using 1.0 ml or 1.0 g samples. Preliminary pharmacokinetic parameters of fluoride obtained in two subjects are reported.

Pharmacokinetics of a single dose of ofloxacin in healthy elderly subjects using noncompartmental and compartmental models

The pharmacokinetics of ofloxacin following a single 200 mg oral dose were studied in twelve healthy elderly volunteers. Relevant pharmacokinetic parameters were analysed by both noncompartmental and compartmental models. In compartmental analysis, the data on plasma concentrations was best described by an open two-compartment model. A zero-order absorption behaviour was found in some volunteers. The terminal half-lives were slightly prolonged and ranged from 6.2–11.6 h. A linear relationship was found between the renal clearance of the drug and the estimated creatinine clearance. Computer predictions of a multiple 200 mg dose regimen showed no important accumulation of ofloxacin. The recommendation of some authors that, in general, ofloxacin dosage may be halved in the elderly could not be confirmed. This has to be determined through further clinical experience in elderly ill subjects.

A ready-to-use activated charcoal mixture. Adsorption studies in vitro and in dogs: its influence on the intestinal secretion of theophylline in a rat model.

A practical, ready-to-use preparation of activated charcoal (AZU mixture) for application in toxicology has been formulated. Tb establish its efficacy, the formulation was testedin vitro and in dogs. Thein vitro adsorption capacity was compared to that of freshly prepared charcoal suspension in water (CW) and to Carbomix®. Langmuir adsorption coefficients demonstrated small but clinically insignificant differences in adsorption capacity between the preparations. The laxative sodium sulfate did not reduce the adsorption capacity of charcoalin vitro. Dogs were given 60 mg of paracetamol per kg as an oral solution followed by 5 g of activated charcoal preparation. The area under the plasma concentration versus time curve (control 2955±353 mg·min−1·1−1) was significantly reduced following CW (921±453) and AZU (786±270). The premixed AZU charcoal formulation is efficacious, inexpensive and overcomes the problems of bed-side preparation. An isolated vascularly perfused rat small intestine can be used to describe the effect of activated charcoal on the intestinal secretion of theophylline.

The Influence of Extracorporeal Clearance Techniques on Elimination of Radiocesium after Internal Contamination

Radiocesium, an isotope released after nuclear accidents such as Chernobyl, causes damage to the health of humans after internal contamination. As a result of an internal deposit of radiocesium these persons are continuously irradiated and noxious effects may occur. Removal of this internal radiation source will reduce immediate (short-term) and future damage (long-term). In order to obtain data with respect to cesium kinetics in vivo, data obtained in dogs by Nold et al. were fitted by a computer program. On the basis of these data, simulations were carried out to evaluate the influences of extracorporeal clearance on cesium kinetics. The influence of various treatments on the committed effective dose [E(50)] as a measure of radiation harm was simulated. For this purpose an equivalence between the committed effective dose and the area under the curve, a kinetic parameter, was derived. This equivalence only holds when comparisons are made for different treatments of one subject contaminated with one isotope. Treatment with orally administered Prussian Blue salts reduces the committed effective dose by 29% (50 y). This can be insufficient to prevent deterministic effects as a result of a severe internal contamination with radiocesium. For this purpose other methods are evaluated. In simulations, extracorporeal clearance (e.g. hemoperfusion or hemodialysis) proved to be more effective in reducing E(50) (> 50%, 50 y). Extracorporeal clearance also seems to be effective in the early dose reduction and its consequent deterministic effects. Simulations revealed that effectiveness is improved when the treatment is started earlier and continued for a longer period. Effective extracorporeal clearance may be considered to be a promising method to treat victims of nuclear accidents internally contaminated with radiocesium.

Hemodialysis as a potential method for the decontamination of persons exposed to radiocesium

Radiocesium may be deposited in the environment as a result of accidents in nuclear installations, for example, as in Chernobyl. Significant internal contamination with radiocesium poses a serious risk to human health, and, therefore, expedient removal is essential to reduce the radiation body burden. In vitro hemodialysis was tested as a potential method to remove radiocesium from a pasteurized plasma solution of bovine or human blood. Clearance values were calculated by a flow independent method. Hemodialysis appears to be a good method to remove radiocesium from blood: within 4 h more than 90% of the administered radiocesium is removed from blood or plasma. Radiocesium in dialysis fluid can be concentrated on Prussian Blue coated columns that were tested previously for hemoperfusion. Radioactive waste disposal problems can be solved by concentration of radiocesium on these columns. In vivo experiments are necessary to confirm these in vitro results.

Compatibility of bupivacaine and iohexol in two mixtures for paediatric regional anaesthesia

The compatibility of bupivacaine (0.25% and 0.125% wt/vol) with iohexol 300 mg I/ml was investigated. At room temperature bupivacaine does not decompose in these mixtures over a period of 24 h. pH Values (7.10 and 7.33), clarity, osmolality (370 and 379 mOsm/kg) and buffer capacity (0.035 ml and 0.010 ml 0.1000 mol/l NaOH per 10 ml) meet requirements for epidural injection. Both mixtures are suitable for epidurography.

A general system for the automation of a backflush equipped gas chromatograph and its application in the determination of fluoride in plasma and faeces

A fully automated system is described in which a gas chromatograph equipped with a backflush valve is automatically operated under the control of a specially designed timer unit. The system requires minimum data acquisition due to the selection of the signals to be integrated while waste of recorder paper is also avoided. It has the capability of unattended operation of fifty samples which — in the case of fluoride determination — are chromatographed in about four hours.