The kinetics of ceftriaxone, a cephalosporin, was studied in six healthy subjects who received bolus injections of 150, 500, and 1,500 mg intravenously in a random crossover fashion. Although total drug concentration time profiles after all doses could be described by biexponential equation, simple compartment analysis was inappropriate because a disproportional increase in the area under the total drug concentration time curves occurred with dose. This resulted in a dose-dependent increase in total systemic clearance (ClTS) from 9.7 ml/min at the 150-mg dose to 13 ml/min at the 1500-mg dose. The dose-dependent changes in ClTS could be explained in terms of the concentration-dependent plasma protein binding of ceftriaxone (fplasma ranging from 0.04 to 0.167), because the area under the free drug concentration time curves (AUCFO-infinity) increased proportionately to dose. Mean total clearance with reference to free (unbound) ceftriaxone (ClFS) was constant at 255 ml/min. Calculated mean renal clearance with reference to free ceftriaxone (ClFR) was 173 ml/min, or slightly more than the average glomerular filtration rate in humans. Mean plasma ceftriaxone t1/2 was not influenced by dose and averaged 8 hr. This biological t1/2 is by far the longest ever for a cephalosporin in healthy subjects.

This report summarizes the results of three pharmacokinetic studies of cefetamet and cefetamet pivoxil conducted in normal adult male volunteers. In the first study the pharmacokinetics of cefetamet were evaluated after intravenous infusion of doses ranging from 133 to 2,650 mg. Over this dose range, the pharmacokinetics were linear. A dose-proportional increase in the area under the curve from zero to infinity was observed, whereas total clearance (140.3 ± 23.6 ml/min), renal clearance (130.3 ± 18.2 ml/min), volume of distribution at steady state (0.288 ± 0.023 liter/kg), fraction excreted unchanged in the urine (94 ± 11%), and elimination half-life (2.07 ± 0.18 h) were independent of dose. In a second study the absolute bioavailability of single 1,500-mg doses of a tablet formulation of the pivaloyloxymethylester of cefetamet was evaluated under conditions of fasting and after a standard breakfast. Administration with food increased the extent of absorption (from 31 ± 7 to 44 ± 4 %) while decreasing the rate of absorption (time to maximum concentration of drug in plasma increased from 3.0 ± 0.6 to 4.8 ± 0.4 h). The third study consisted of multiple oral administration of 1,000 mg of a similar oral tablet formulation twice daily for 10 days. This regimen was preceded and followed by intravenous administration of a 500-mg bolus dose of cefetamet. Oral doses were administered with breakfast and dinner. The absolute bioavailability of the tablet formulation was assessed after the first dose and after both the morning and the evening doses on day 10 of oral therapy. The compound was consistently absorbed to the extent of approximately 50% with no significant differences observed between the morning and evening doses on day 10.Cefetamet pivoxil (Fig. 1A) is an orally administered pivaloyloxymethylester of the active cephalosporin compound cefetamet (Fig. 1B). The ester is very lipophilic at neutral pH values (octanol-water partition coefficient of 650 at pH 7.5) but is quite water soluble at pH 2.0 or below (20 mg/ml at pH 1.0 versus 0.16 mglml at pH 5 to 6). Cefetamet possesses a broad spectrum of activity against many aerobic gram-positive and -negative organisms (8). It is more active than current oral cephalosporins against many members of the Enterobacteriaceae family, Haemophilus spp., Neisseria spp., Branhamella catarrhalis, and all nonenterococcal species of streptococci (including penicillin-resistant Streptococcus pneumoniae). Cefetamet possesses virtually no activity against Staphylococcus spp. Given its spectrum of activity, the major clinical indications foreseen for this compound are the treatment of respiratory and urinary tract infections and otorhinolaryngological infections.In this paper we report the results of three pharmacokinetic studies of cefetamet and cefetamet pivoxil. These studies investigated the pharmacokinetics of the active compound after intravenous administration, the bioavailability from the ester compound after single doses administered during fasting and after a standard breakfas...

Abstract. We calculate the color of the Martian sky and surface directly using the absolute calibration of the Mars Pathfinder (MPF) lander camera, which was observed to be stable during the mission. The measured colors of the Martian sky and surface at the Pathfinder site are identical to the Viking sites, i.e., a predominantly yellowish brown color with only subtle variations. These colors are distributed continuously and fall into five overlapping groups with distinct average colors and unique spatial characteristics: shadowed soil, soil, soil/rock mixtures, rock, and sky. We report that the primary difference between the sky color and the color of the rocks is due to a difference in brightness. Measurements of the sky color show that the sky reddens away from the Sun and toward the horizon and that the sky color varies with time of day and is reddest at local noon. We present a true color picture of the Martian surface and color enhancement techniques that increase image saturation, maximize color discriminability while preserving hue, and eliminate brightness variations while preserving the chromaticity of the scene. Although Mars has long been called the "red" planet, quantitative measurements of the surface color from telescopic and surface observations indicate a light to moderate yellowish brown color. The Pathfinder camera measurements presented here support the claim that the red planet is not red but indeed yellowish brown.

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had relatively low binding affinities. 4 The concentration of serum proteins influences both the fraction of unbound drug and the fraction of drug associated with the erythrocytes. Changes in serum protein concentrations often encountered in malaria are likely to increase both the unbound fraction and the fraction bound to the erythrocytes.