Distribution in normal and inflammatory tissue of a new semisynthetic cephalosporin, SK&F 75073.

SK&F 75073 is a new cephalosporin with broad spectrum antibacterial activity. SK&F 75073-14C and cefazolin-35S were administered separately to groups of rats as a single intramuscular dose of 20 mg/kg. Tissues with highest drug levels 15 minutes following dose were as follows: (SK&F 75073/cefazolin levels), kidney - 86/70 microgram/g, liver - 33/22 microgram/g, lung - 29/17 microgram/g, heart - 23/10 microgram/g, adrenal - 13/7 microgram/g. Plasma levels at peak were 134 microgram SK&F 75073/ml (half-life, 1.9 hours) and 72 microgram cefazolin/ml (half-life, 0.75 hours). Dose excreted in 24 hours was: SK&F 75073, urine 66% and feces 27%; cefazolin, urine 96% and feces 2%. Both antibiotics were also administered, at 20 mg/kg, to rats with the carrageenan-induced inflammatory pouches. Exudate from these pouches contained from 2 to 10 times more SK&F 75073 than cefazolin. Radioassay and bioassay of these substances in the exudate gave similar results. Serum protein binding ranged from 96 approximately 98% for SK&F 75073 and 34 approximately 69% for cefazolin. Data indicated that highly protein bound SK&F 75073 enters tissues and tissue fluid to a greater extent than the lesser bound but therapeutically proven antibiotic agent cefazolin.

Bioavailability of cimetidine in man.

The bioavailability of parenteral cimetidine was tested in 12 volunteers in a balanced three-way crossover study. Blood levels and urinary excretion were compared after intramuscular and intravenous injection and oral administration of 300 mg of cinetidine. The results indicated that the intramuscular and intravenous routes are virtually interchangeable for parenteral cimetidine, and that the oral liquid, although exhibiting a reduced area under the blood level curve as compared with the parenteral doses, nevertheless demonstrated equivalence with respect to the time the blood level remained above 0.5 microgram per ml. The 300-mg cimetidine tablet formulation was found in another group of 12 volunteers to be bioequivalent to a 300-mg dose of oral liquid.

High-pressure liquid chromatographic analysis of cimetidine, a histamine H2-receptor antagonist, in blood and urine.

A method is described for extraction of cimetidine, a histamine H2-receptor antagonist, from whole blood and urine with subsequent analysis by high-pressure liquid chromatography (HPLC). The drug is extracted from biological fluids with 1-octanol and back-extracted into dilute acid and then into a small volume of ethanol by saturation with potassium carbonate. HPLC analysis is performed on a column of 5-micrometer silica with a mixed mobile phase consisting primarily of acetonitrile. The method measures concentrations of cimetidine as low as 0.05 microgram/ml and is reproducible. Blood levels and urinary excretion data obtained with the analytical procedure are given for a group of human subjects who received 200-mg oral doses of cimetidine.

Use of anemic piglet to assess bioavailability of iron from oral iron preparations.

Except for methods using long-lived iron isotopes, there are no reliable means for assessing the bioavilability of iron from oral preparations in human subjects. Use of the anemic piglet as an alternative means was studied. When piglets were made anemic on a commercial milk diet and then dosed with solutions of 1, 2, and 5 mg/kg of ferrous sulfate/day, a dose-related recovery of hematocrit and hemoglobin levels resulted. The most sensitive dose range for use in a bioavailability study of iron was between 1 and 2 mg of iron/kg/day when using these parameters. A study carried out using this method indicated that the iron from a delayed-release capsule and from a ferrous sulfate solution was equally bioavailable. Hemoglobin and hematocrit recovery rates of the anemic piglet were shown to be reliable and sensitive indicators of the bioavailability of iron from various iron dosage forms.