The pharmacokinetics offosmidomycin was investigated in animals and humans after parenteral and oral dosing. In dogs the serum concentration was 54.8 ,ug/ml at 0.25 h after an intravenous dose of 20 mg/kg, and the half-life was 1.14 h. Peak concentration was 41.4 ;ig/ml after an intramuscular dose of 20 mg/kg and 16.6 ,g/ ml after an oral dose of 40 mg/kg. In volunteers, the serum concentration 0.25 h after dosing was 157 jig/ml after an intravenous dose of 30 mg/kg, 12.3 ,ug/ml after an intramuscular dose of 7.5 mg/kg, and 2.45 j,g/ml after an oral dose of 500 mg. More than 90% of the given dose was excreted in the 24-h urine in rats and dogs after parenteral dosing with 20 mg/kg. The 24-h urinary recovery was 45.8% of the given dose in rats after oral dosing with 100 mg/kg and 37.8% in dogs after oral dosing with 40 mg/kg. In volunteers 85.5% of the intravenous dose (30 mg/kg), 66.4% of the intramuscular dose (7.5 mg/kg), and 26.0% of the oral dose (500 mg) were excreted unchanged in the 24-h urine. In the multiple-dose study, there was no accumulation of fosmidomycin in the serum even after 21 consecutive intramuscular dosings of 1 g every 6 h or 29 consecutive 0.5-h drip infusions of 2 g every 6 h. Biliary excretion was extremely low in rats. Fosmidomycin was well distributed to the tissues of rats after parenteral and oral dosing. The lymph concentrations in dogs were nearly the same as serum concentrations. Serum protein binding was low (4% or less) to mouse, rat, dog, and human serum.
Exposure of the tissue to be operated on is of central importance to the success of surgery. Operation on the mitral valve rnay be difficult when exposure is not satisfactory, as is the case when the left atrium is not enlarged or the atrioventricular ring is adhering to the pericardium because of a previous operation. By using video-assisted visualization in combination with direct observation, we were able to achieve a highly satisfactory view of the mitral valve in all such cases. We describe a method of
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