1. Population pharmacokinetic parameters of tobramycin were determined in a heterogenous group of 97 patients using serum samples drawn for the routine monitoring of tobramycin concentrations, following multiple dosing regimens. 2. To describe the accumulation kinetics of tobramycin a two‐compartment pharmacokinetic model was required. The best fit to the data was obtained when drug clearance (1 h‐1) was related linearly to creatinine clearance (proportionality constant: 0.059 +/‐ 0.002 x CLcr (ml min‐1)) and initial volume of distribution (1) was related linearly to body weight (proportionality constant: 0.327 +/‐ 0.014 x body weight (kg)). The intersubject variability in these two parameters was 32% and 3%, respectively, whilst the residual or intrasubject variability amounted to 21% of the tobramycin concentration. The terminal half‐life of tobramycin, 26.6 +/‐ 9.4 h, was appreciably shorter than previously reported. 3. The population pharmacokinetic model was validated against data obtained from 34 independent patients and the predicted and observed concentrations were found to be in good agreement. The population pharmacokinetic model was used to design a priori dosing recommendations for tobramycin.

EXPOSE-R flew as the second of the European Space Agency (ESA) EXPOSE multi-user facilities on the International Space Station. During the mission on the external URM-D platform of the Zvezda service module, samples of eight international astrobiology experiments selected by ESA and one Russian guest experiment were exposed to low Earth orbit space parameters from

On July 23, 2014, the Progress cargo spacecraft 56P was launched from Baikonur to the International Space Station (ISS), carrying EXPOSE-R2, the third ESA (European Space Agency) EXPOSE facility, the second EXPOSE on the outside platform of the Russian Zvezda module, with four international astrobiological experiments into space. More than 600 biological samples of archaea, bacteria (as biofilms and in planktonic form), lichens, fungi, plant seeds, triops eggs, mosses and 150 samples of organic compounds were exposed to the harsh space environment and to parameters similar to those on the Mars surface. Radiation dosimeters distributed over the whole facility complemented the scientific payload. Three extravehicular activities later the chemical samples were returned to Earth on March 2, 2016, with Soyuz 44S, having spent 588 days in space. The biological samples arrived back later, on June 18, 2016, with 45S, after a total duration in space of 531 days. The exposure of the samples to Low Earth Orbit vacuum lasted for 531 days and was divided in two parts: protected against solar irradiation during the first 62 days, followed by exposure to solar radiation during the subsequent 469 days. In parallel to the space mission, a Mission Ground Reference (MGR) experiment with a flight identical Hardware and a complete flight identical set of samples was performed at the premises of DLR (German Aerospace Center) in Cologne by MUSC (Microgravity User Support Center), according to the mission data either downloaded from the ISS (temperature data, facility status, inner pressure status) or provided by RedShift Design and Engineering BVBA, Belgium (calculated ultra violet radiation fluence data). In this paper, the EXPOSE-R2 facility, the experimental samples, mission parameters, environmental parameters, and the overall mission and MGR sequences are described, building the background for the research papers of the individual experiments, their analysis and results.

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Amiloride hydrochloride labeled with C14 was given to 5 volunteers. Serum level peaked at 3 hours, and the half‐life was 6 hours. There was no evidence of metabolic transformation of amiloride. Approximately half the oral dose was recovered in the urine. Amiloride is cleared by tubular transport and should be used with caution in patients with renal insufficiency.