The pharmacokinetics of spectinomycin hydrochloride after 2 g intravenous doses were studied in ten volunteers with varying degrees of renal function. Mean peak serum concentration in 8 volunteers with renal insufficiency was 150.9 ± (SD) 42.3 μg/ml which was similar to 2 normal volunteers who had concentrations of 139 and 186 μg/ml. Serum half-lives in the volunteers with renal insufficiency ranged from 4.7 to 29.3 h and increased as creatinine clearance decreased. Serum half-lives of the 2 normal volunteers were 1.5 and 1.7 h. Urine concentrations and percents of recovery were variable.
Mezlocillin and carbenicillin were administered intravenously to healthy male volunteers, for six days each, in a double-blind crossover study. Tests to detect abnormalities in haemostasis were performed before, during and after administration. Platelet aggregation studies indicated that both antibiotics interfered with platelet aggregation and secretion resulting in prolonged bleeding times. The effect was dose related and rapidly reversible after discontinuation of the antibiotics. It always occurred earlier and was more profound with carbenicillin than with mezlocillin (P = 0.008). Bleeding times greater than 15 min were observed in 17% of volunteers who received 18 g/day of mezlocillin and 83% of volunteers who received 18 g/day of carbenicillin (P less than 0.05). There were no abnormalities in the coagulation cascade. The risk of acquiring an antibiotic-induced clinical bleeding disorder is lower with mezlocillin than with carbenicillin.
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SummaryIn 35 normal rabbits the cerebrospinal fluid glucose values ranged between 56 and 135 mg/dl, mean and standard deviation 78 ± 13 mg/dl. Cerebrospinal total protein values ranged from 16 to 66 mg/dl, mean and standard deviation 33 ± 10 mg/dl. The mean values were similar to those reported for human cerebrospinal fluid. Depression of the cerebrospinal glucose level in the rabbit may parallel the human situation and prove to be a useful marker of purulent inflammation.The rabbit model of human meningitis has recently received renewed attention (Delgado Phillips & A vent, 1978; Mitchell, Hinthorn & Liu, 1978; Scheid, Fletcher, Fink & Sande, 1978), and Sorensen, Breen & Benzler (1973) described the cerebrospinal protein, lactic dehydrogenase and cell count in the normal rabbit, and contrasted these values with those obtained after experimental meningeal inflammation. It is well known that the cerebrospinal glucose value is very low in purulent meningitis in man (Thorn, Adams, Braunwald, Isselbacher & Petersdorf, 1977), and it would be helpful to know the normal baseline values in rabbits for experimental reference. To our knowledge this information is not readily available (Jones, 1975 fluid analysis as they utilize small quantities of test fluid (0.2 ml for protein determination and 0.1 ml for glucose determination).Results 35 rabbits were subjected to intraventricular puncture to obtain cerebrospinal fluid. 9 rabbits underwent multiple puncture for protein determination. In 2 rabbits the protein level and in 1 rabbit the glucose level were not measured. The remaining 23 rabbits had a single intraventricular puncture for both protein and glucose determinations. The mean glucose value (± 1 s.d.) was 78 ± 13 mg/dl, with N = 50 (N = total number of determinations
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