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A rapid intravenous bolus injection of cephazolin (4.0 g) was administered immediately before induction of anaesthesia to seven patients having total hip replacement. The plasma, bone, hip capsule and drain fluid concentrations of cephazolin following rapid intravenous injection of cephazolin were all well above the minimum bactericidal concentration of this antibiotic against a wide range of organisms, in particular, the penicillin resistant Staph. aureus, most Gram negative rods and Bacteroides species that cause postoperative infections in these patients. These results suggest that an intravenous bolus injection of cephazolin (4.0 g) given during induction of general anaesthesia should provide safe, effective prophylactic cover against all the organisms that cause postoperative wound infections in patients who undergo total hip replacement. This pharmacokinetic finding needs to be confirmed in a larger clinical trial of cephazolin. The optimum empirical prophylactic mode of administration of cephazolin that provides high plasma and tissue concentrations during this procedure appears to be a rapid intravenous bolus injection before induction of anaesthesia. The intravenous injections of cephazolin were well tolerated in every patient. No cases of thrombophlebitis occurred and no other side or toxic effects were reported.

SummaryAs the pharmacokinetics after a slow infusion had not previously been evaluated in the doses used in this study, it was decided to measure the plasma concentration/time curve after a twelve-hour intravenous infusion of 2-0 g of erythromycin lactobionate in 2 litres of 0.9/o normal saline. Six healthy medical students with no past history of cardiovascular, renal, hepatic, metabolic or gastrointestinal disease and no past drug allergy participated. The concentration of erythromycin base in venous blood was measured by small plate microbiological assay. Venous blood was taken at zero, 15, 30, 45, 60 min and at 2, 3, 4, 6, 8, 12, 16, 20 and 24 hr after starting the infusions. Duplicate assays were performed on all plasma samples at Guy's and at the manufacturer's laboratories. A full haematological and biochemical screening profile was performed before and after the study. The mean + s.e. plasma erythromycin base concentration rose from 0.7 ± 0'2 jig/ml at 15 min to 6.06 ± 1.6 jg/ml at 1 hr. The peak plasma concentration was between 1.48 ± 0-25 jig/ml at 30 min and 7-21 + 0.93 jig/ml at 4 hr. The plasma concentration at 12 hr was 6.17 + 0.33 pg/ml, and fell to 037 ± 0.05 jtg/ml at 24 hr.These findings suggest that therapeutically effective plasma concentrations follow a slow intravenous infusion of erythromycin lactobionate. There was no evidence of adverse haematological or biochemical function in the tests of blood, hepatic or renal function, apart from two volunteers who vomited after the infusions were discontinued.

compared with those using the diaphragm when they refer to these two conditions occurring among users of the oral contraceptive ? I would be grateful if this point could be clarified as the text does not do so.