Single-dose ceftriaxone kinetics in liver insufficiency

The disposition profile of ceftriaxone was studied in eight normal subjects and in 15 subjects with various degrees of chronic liver damage (alcoholic fatty liver [FL] and cirrhosis without [C] and with [CA] ascites) who received bolus injections of ceftriaxone, 1 gm iv. Plasma protein binding fell in all. As a result, mean free fraction in plasma rose between 140% (FL) and 320% (CA). An exceptionally large rise (1270%) occurred in one subject with CA when the condition was aggravated by renal impairment. Fourteen of 15 subjects had renal clearance of unbound drug of the same order as that in healthy adults. In chronic liver disease, mean nonrenal clearance of unbound drug fell with severity of liver damage. Kinetic parameters with reference to total drug differed in normal subjects and subjects with CA. Kinetic changes in the latter were such that elimination t 1/2 beta did not differ (9.7 and 8.4 hr). Because of the wide therapeutic range of ceftriaxone, subjects with chronic liver disease would require no dose adjustments, whereas dose reductions are envisaged for subjects with cirrhosis (C,CA) on the basis of increased unbound drug concentrations.