Furosemide kinetics were studied in normal volunteers and patients with renal failure. Comparison of results from intravenous bolus and intravenous infusion in normal subjects showed no significant model dependency of estimations of furosemide clearance, although the average clearance by fitting to a one-compartment model was 16% higher than that obtained by fitting to a two-compartment model. Normal subjects had a total body clearance of furosemide of 1.53 +/- 0.11 (SE) ml/min/kg, a volume of the central compartment of 2.61 +/- 0.37 L, a volume of the peripheral compartment of 2.48 +/- 0.24 L, and a half-life of 0.8 +/- 0.06 hr and they absorbed 68.9% +/- 7.1% of a solution of furosemide given by mouth. The corresponding values in patients with renal failure were 0.27 +/- 0.03 ml/min/kg, 8.02 +/- 0.96 L, 14.1 +/- 3.57 L, 14.2 +/- 2.30 hr, and 43.4% +/- 8.0%, all differing significantly different from the normal. The bioavailability of 500-mg tablets of furosemide in the renal failure patients was 43.4% +/- 7.4%, equivalent to the absorption of the dose given to the same patients in the form of a solution.

SUMMARYThe effect of an environmental temperature of 28-30' C. and a relative humidity of 35-45 per cent on the protein metabolic response to injury of one or more major long bones of the lower limbs has been studied in 29 male patients and 28 similar controls housed at 20-22OC. The metabolic response was reduced at the higher temperature compared with the controls, the more severely injured showed a greater metabolic response than the less severely injured, and the ameliorating influence of environmental temperature was more noticeable in the former. The metabolic response seems to be principally one of catabolism of muscle, with increased urinary excretions of potassium, creatine, and zinc in the urine correlating well with those of nitrogen at 20" C. but not at 30' C. The response (i.e., catabolism of muscle) was not affected by post-injury diet at 2 0 ' C. ambient temperature. There was a reduction in the disturbance of the plasma proteins.In general, the patients tolerated the warm drier conditions. Owing to the intrinsic difficulty in assessing minor changes in bone healing it was not possible to assess what, if any, beneficial change occurred in the fracture site. From our experimental observations on the rat and the work of others on burned patients the reduction in heat production at the higher ambient temperature is accompanied by an enhanced rate of healing of surface wounds.THE metabolic response to injury is both local and general. It is with the latter in its post-shock manifestations following moderate to severe physical injury to the limbs of man that this report is concerned, and, in particular, with the effect on this response of raising the environmental temperature to the zone of 68 thermoneutrality for clothed man (28-30' C.). This topic has been of considerable interest to those working in the field of metabolic response to trauma

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The pharmacokinetics of metolazane (Zaroxolyn)