The diversity of tectonic modes and thoughts about transitions between them.

Plate tectonics is a particular mode of tectonic activity that characterizes the present-day Earth. It is directly linked to not only tectonic deformation but also magmatic/volcanic activity and all aspects of the rock cycle. Other terrestrial planets in our Solar System do not operate in a plate tectonic mode but do have volcanic constructs and signs of tectonic deformation. This indicates the existence of tectonic modes different from plate tectonics. This article discusses the defining features of plate tectonics and reviews the range of tectonic modes that have been proposed for terrestrial planets to date. A categorization of tectonic modes relates to the issue of when plate tectonics initiated on Earth as it provides insights into possible pre-plate tectonic behaviour. The final focus of this contribution relates to transitions between tectonic modes. Different transition scenarios are discussed. One follows classic ideas of regime transitions in which boundaries between tectonic modes are determined by the physical and chemical properties of a planet. The other considers the potential that variations in temporal evolution can introduce contingencies that have a significant effect on tectonic transitions. The latter scenario allows for the existence of multiple stable tectonic modes under the same physical/chemical conditions. The different transition potentials imply different interpretations regarding the type of variable that the tectonic mode of a planet represents. Under the classic regime transition view, the tectonic mode of a planet is a state variable (akin to temperature). Under the multiple stable modes view, the tectonic mode of a planet is a process variable. That is, something that flows through the system (akin to heat). The different implications that follow are discussed as they relate to the questions of when did plate tectonics initiate on Earth and why does Earth have plate tectonics.This article is part of a discussion meeting issue 'Earth dynamics and the development of plate tectonics'.

[Changes in plasma proteins and drug distribution in kidney and liver diseases]. / Promjene plazmatskih proteina u bolestima bubrega i jetre i distribucija lijekova.

Kidney and liver diseases induce alterations in drug binding to plasma proteins. These alterations are caused by qualitative and quantitative changes of plasma proteins and the presence of endogenous substances which act as competitive inhibitors of drug binding to plasma proteins. These changes are the most prominent in nephrotic syndrome and uremia among kidney diseases and in cirrhosis among liver diseases. The more important drugs in which the free fraction is changed in these entities are listed in the tables. The changes in drug distribution caused by plasma protein alterations may induce significant changes in entire drug pharmacokinetics. Discussed are theoretically expected and experimentally proven changes in plasma proteins in kidney and liver diseases and their influence to drug action and dosing regimen.

Evaluation of slow-release theophylline pharmacokinetics by Fourier's harmonic analysis.

Theophylline absorption from two sustained-release theophylline formulations was examined over 2 consecutive days during continuous therapy in 7 asthma patients. We compared two twice daily formulations of Teotard capsules (TC) and Teolin tablets (TT). Bioavailability for each 12-h period was defined as: BIO = (AUC oral/AUC iv) x (Dose iv/Dose oral)x100. The amount of theophylline absorbed during each 2-h interval was calculated using modified Wagner-Nelson equation for multiple dose drug administration. Mean serum theophylline concentrations were analysed by Fourier's harmonic analysis (FHA) and by F test. There were not statistically significant differences between TT and TC neither for BIO nor for fractional absorption calculated for 2-h sampling intervals. On the other hand FHA of mean SCT disclose more predictable theophylline absorption from TT compared to TC. We conclude that in order to obtain complete pharmacokinetic profile of slow-release formulation FHA should also be included into the calculations.

[Pharmacokinetics of Teolin 300 tablets and Teotard 350 capsules in asthma patients]. / Farmakokinetika tableta Teolin 300 i kapsula Teotard 350 u astmaticara.

Pharmacokinetics of tablets Teolin 300 (TT) and capsules Teotard 350 (TC) was studied in 7 asthma patients. Serum theophylline concentrations (SCT) were measured in 2-h intervals over 2 consecutive days for each theophylline formulation. A randomized, crossover design was used. In 12-h one dose of TT was absorbed 89.76 +/- 32.76% (means +/- SD) and TC 83.76 +/- 49.48%; between them there were statistically no differences. Amplitudes of SCT (AMP) were in the range 0.31 to 2.7 and mean 24-h SCT in the range 19.8 to 119.3 mumol/L. AMP were reproducible only to TT (r = 0.97, p less than 0.001). Fourier's harmonic analysis applied to mean SCT disclosed statistically significant 12-h oscillations only for TT (p less than 0.05). Continuous therapy with slow-release theophylline should always be monitored with measurements of SCT which should be interpreted by pharmacokinetics data of applied sustained theophylline formulation.

Bioavailability of dihydroergosine in healthy volunteers.

Eight healthy volunteers received an oral dose of 10 mg and an intravenous dose of 0.75 mg of dihydroergosine. Plasma concentrations were measured by HPLC method, and some pharmacokinetic parameters were calculated. The biologic half-life in the elimination phase was 8.35 +/- 1.87 h after oral administration and 8.84 +/- 3.64 h after intravenous administration. In both cases of administration a secondary rise in plasma concentration of dihydroergosine was observed, which can be attributed to hepatic recycling. The calculated bioavailability of the drug was 9.80 +/- 2.8%.

Dose-dependent bioavailability of propranolol.

The pharmacokinetics of orally administered propranolol in doses of 10, 40, 80 and 160 mg was studied in eight healthy volunteers in a cross-over trial. The analytical method applied made possible a parallel determination of propranolol and of 4-OH propranolol. The dose-dependent kinetics of orally administered propranolol was demonstrated. In our study linear dependence could be established only within a dosage range of 40 mg to 160 mg. Both substances determined in plasma, propranolol as well as 4-OH propranolol, show a tendency toward non-linearity, particularly at the lower dosage range between 10 and 40 mg.

Pharmacokinetics of dihydroergosine in rats after intravenous and oral administration.

Wistar rats received an intravenous dose of 20 micrograms/kg and an oral does of 40 micrograms/kg 3H-Dihydroergosine. Concentrations of radioactivity were measured in plasma, bile, urine, and faeces, and pharmacokinetical parameters of an open two compartment model were calculated. After intravenous injection and oral administration 3H-Dihydroergosine is rapidly lost from the central compartment with distribution rate constants alpha = 0.889 h-1 and beta = 0.722 h-1, respectively. Biological half life in the elimination phase after both application is nearly the same t 1/2 = 13.6 h. The volume of central compartment is Vc = 3.075 l/kg and the volume of distribution Vd beta = 30.75 l/kg. The fraction of 3H-Dihydroergosine absorbed after oral administration, calculated from areas under the curves upon oral and intravenous administration, is 31%. The percentage of 3H-radioactivity eliminated with bile was 98.3% of the dose within 72 hours after intravenous and 29.3% after oral administration. The main portion of the administered 3H-radioactivity was recovered in faeces -66.1% after intravenous and 81.3% after oral administration, while only 17.4% and 4.9% of the administered dose was eliminated in the urine within 120 hours, respectively.

Dihydroergosine pharmacokinetic modelling and simulation.

For this study of dihydroergosine pharmacokinetic modelling and simulation, the data from our paper about 3H-DHESN plasma, bile, urine, and faeces concentrations after intravenous and oral administration were used (1). The model obtained with the identified parameters was in agreement with in vivo data. Certain special phenomena, such as the enterohepatic cycle and incomplete absorption, were taken into account. Analog-hybrid simulation and identification represents an effective tool for such studies. In spite of the limited validity of the available in vivo data, the work represents a first step in the introduction of DHESN into human medicine.