Levels of the isoxazolyl penicillins, cloxacillin and flucloxacillin, in serum and synovia of horses

Abstract

Cloxacillin and flucloxacillin were administered to horses by single intravenous dose (25, 33 or 44 mg/kg). Levels of these compounds were assayed biologically from serum and synovia of the carpal and tibio‐tarsal joints at intervals up to 360 min. Serum levels of cloxacillin at 30 min were all in excess of 48 μg/ml and were equal to, or higher than, those given by the equivalent doses of flucloxacillin. Highly significant differences (P<0.001) between doses and between sampling times (30, 60, 90, 120, 180, 240, 360 min) were detected for both compounds. Although the rates of elimination of cloxacillin and flucloxacillin from blood did not differ significantly, the early establishment of higher levels of cloxacillin in blood meant that it regularly persisted longer than flucloxacillin in both serum and synovia. The rate of elimination from serum was significantly steeper (P<0.001) than that computed for synovia. The slower rate of loss of cloxacillin or flucloxacillin from the synovia than the blood appears to fit the model of transfer between serum and synovium proposed by Howell, Sutherland & Rolinson (1972). The persistence of cloxacillin and flucloxacillin in synovia beyond the time when effective minimum inhibitory concentrations (4 μg/ml) were present in the blood, indicates a practical advantage in equine therapeutics where septic arthritis is the major indication for use of these compounds. In these situations, cloxacillin has a further clinical advantage in persisting in synovia for a longer time than flucloxacillin.

Actions of calcitonin, parathyroid hormone, and prostaglandin E2 on cyclic AMP formation in chicken and rat osteoclasts

“…It0 et al [36] studied the PTH effect closely in chick osteoclast cultures and found that greater cyclic AMP responses to PTH occurred in cultures with greater degrees of contamination by alkaline phosphataserich cells. Our conclusion from that work [36] and our own data is that PTH does not increase cyclic AMP formation in either rat or chick osteoclasts; it is consistent with the view that the PTH response occurred in osteoblast-like cells and that the target cells in bone for the effect of PTH on cyclic AMP are exclusively cells of the osteoblast lineage [5,33].…”

“…Finally, the results with PTH warrant comment. The fact that both PTH and calcitonin increase cyclic AMP production in bone has been explained by the PTH effect taking place in osteoblasts and the calcitonin effect in osteoclasts [33], but this has never been demonstrated directly until the present study. A biochemical response to PTH was noted in impure osteoclast cultures derived from both rat and chick, but PTH did not influence cyclic AMP formation in osteoclasts from either species as detected by immunocytochemistry.…”

“…In the present work we have shown that the chick osteoclast does not respond to calcitonin with a rise in cyclic AMP. In view of the role ascribed to cyclic AMP in calcitonin action on osteoclasts [32,33], this seemed a surprising finding. However, it is consistent with preliminary data obtained by others with chick cells prepared in a similar way [34], with studies of calcitonin effects on avian bone [35] and on freshly isolated osteoclasts from 15-to 24-day-old chick metatarsi [36].…”

Pharmacokinetics of amoxycillin in normal horses and horses with experimental arthritis

“…When using systemically administered therapy, however, there must be certainty that adequate concentrations of the therapeutic agent are attained in the infected tissue and joint space. Many studies of synovial fluid antibiotic levels after systemic administration have been conducted in horses (Beech et al ., 1977; Beech et al , 1979; Martin et al , 1980; Stover et al , 1981a,b; Brown et al , 1982; Soraci et al , 1996). Normal horses were used in all of these pharmacokinetic studies.…”

Farmacocinética sérica y sinovial de amoxicilina en equinos sanos y con artritis aséptica inducida

“…Esto marca algunas diferencias con lo hallado para otros antibióticos betalactámicos en sinovia de equinos, como en el caso de cefapirina, en la que se reportó 4.6 pg/ml de concentración máxima (Brown et al, 1986), o tal como se reportó para cloxacilina, para la cual se hallaron concentraciones máximas de 4 gg/ml (Martin et al, 1980).…”