The absolute bioavailability and lung tissue distribution of the triamilide antimicrobial, tulathromycin, were investigated in swine. Fifty-six pigs received 2.5 mg/kg of tulathromycin 10% formulation by either intramuscular (i.m.) or intravenous (i.v.) route in two studies: study A (10 pigs, i.m. and 10 pigs, i.v.) and study B (36 pigs, i.m.). After i.m. administration the mean maximum plasma concentration (C(max)) was 616 ng/mL, which was reached by 0.25 h postinjection (t(max)). The mean apparent elimination half-life (t(1/2)) in plasma was 75.6 h. After i.v. injection plasma clearance (Cl) was 181 mL/kg.h, the volume of distribution at steady-state (V(ss)) was 13.2 L/kg and the elimination t(1/2) was 67.5 h. The systemic bioavailability following i.m. administration was >87% and the ratio of lung drug concentration for i.m. vs. i.v. injection was > or =0.96. Following i.m. administration, a mean tulathromycin concentration of 2840 ng/g was detected in lung tissue at 12 h postdosing. The mean lung C(max) of 3470 ng/g was reached by 24 h postdose (t(max)). Mean lung drug concentrations after 6 and 10 days were 1700 and 1240 ng/g, respectively. The AUC(inf) was 61.4 times greater for the lung than for plasma. The apparent elimination t(1/2) for tulathromycin in the lung was 142 h (6 days). Following i.m. administration to pigs at 2.5 mg/kg body weight, tulathromycin was rapidly absorbed and highly bioavailable. The high distribution to lung and slow elimination following a single dose of tulathromycin, are desirable pharmacokinetic attributes for an antimicrobial drug indicated for the treatment of respiratory disease in swine.
SYNOPSIS The relative roles of pressure deformation and ischaemia in the production of compression nerve lesions remain a controversial issue. This paper concerns the genesis of the structural changes which follow compression of the median nerve in the carpal tunnel. The initial lesion is an intrafunicular anoxia caused by obstruction to the venous return from the funiculi as the result of increased pressure in the tunnel. This leads to intrafunicular oedema and an increase in intrafunicular pressure which imperil and finally destroy nerve fibres by impairing their blood supply and by compression. The final outcome is the fibrous tissue replacement of the contents of the funiculi.In 1862 Waller described the motor, vasomotor, and sensory changes which followed the compression of nerves in his own arm. His account carried no reference to the mechanism responsible for blocking conduction in the nerve fibres, presumably because he regarded it as obvious that pressure was the offending agent.Interest in the effects of nerve compression was not renewed until the 1920s when cuff or tourniquet compression was used to produce a reversible conduction block in the nerve. These investigations were confined to a study of the physiological effects of compression and, though they were not concerned with the pathological changes in the nerve responsible for them, they inevitably led to speculation on possible mechanisms and raised the question of whether the block was due to mechanical deformation or to ischaemia introduced by the compression.Many concluded that ischaemia was the responsible agent (Lewis et al
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