In a single-dose tolerance and pharmacokinetics study, enoxacin doses ranging from 200 to 1600 mg were administered orally to 12 healthy normal volunteers. Plasma assays demonstrated rapid absorption of enoxacin with first-order elimination and a half-life averaging 3.4-6.4 h. Renal clearance accounted for approximately 40% of total body clearance of drug. In a second placebo-controlled study, 18 normal volunteers received enoxacin in doses of 400, 600 or 800 mg twice daily for 14 days. Plasma concentrations and pharmacokinetic parameters obtained after the first dose were not significantly different from those observed in the single-dose study. With repeated administration, steady-state plasma concentrations were achieved in three days or less. Steady-state pharmacokinetics were characterized by prompt absorption, first-order elimination, and high urinary concentrations of enoxacin. The most frequently-reported adverse experiences involved the gastro-intestinal tract, the central nervous system, and the skin.

Annals of the Rheumatic Diseases, 35, 446-450. Demonstration of antibodies to collagen and of collagen-anticollagen immune complexes in rheumatoid arthritis synovial fluids. Twenty-nine synovial fluids from patients with rheumatoid arthritis (RA) and 10 synovial fluids from patients with other joint diseases were investigated with regard to the presence of antibodies to denatured human collagen and of collagen-anticollagen immune complexes. 12 of the 29 RA synovial fluids showed anticollagen titres from 1: 16 to 1: 512 in passive haemagglutination. Only one patient in the group with no arthritis had a significant anticollagen titre of 1: 32. Digestion of the synovial fluids with bacterial collagenase resulted in an anticollagen titre increase from two to four dilution steps in 9 of the RA fluids, while 6 previously negative RA synovial fluids showed anticollagen titres from 1: 32 to 1: 128 after digestion with collagenase. These results indicate the existence of collagen-anticollagen immune complexes in 15 of the 29 RA synovial fluids investigated.

In patients suffering from ankylosing spondylitis (AS) HLA-B27 determination by means of the microlymphocytotoxicity test (MLCT) sometimes gives equivocal or false-negative results even though it has been performed with meticulous care. These failures of the test did not arise when the isolated mononuclear cells (MNC) were incubated in lymphocyte culture medium at 37 degrees C under sterile conditions for 24 h. To objectify these observations two methods of HLA class I typing were implemented before and after incubation of the test MNC in culture medium: a bioluminescence method based on the loss of adenosine triphosphate (ATP) in lysed cells in a modification of the usual MLCT and a flow cytometric (FC) test using direct immunofluorescence with an anti-HLA-B27 monoclonal antibody (MAB). In this study 50 patients with AS and 12 healthy volunteers were typed by the usual MLCT according to the NIH standard method and with both of the quantitative methods. In most of the AS patients the discrimination between positive and negative typing results became more distinct after 24 h incubation in culture medium. In the entire group of AS patients tested three false-negative typing results were prevented by this method. Although the MAB against HLA-B27 is cross-reactive with HLA-B7 and HLA-B22, errors in the FC analysis could be avoided by calibration of the flow cytometer with standard calibration beads. Possible explanations for masking of the HLA-B27 in AS patients are discussed.